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1
McPherson, David L., and Mimi T. Salamat. "Interactions among Variables in the P300 Response to a Continuous Performance Task in Normal and ADHD Adults." Journal of the American Academy of Audiology 15, no. 10 (November 2004): 666–77. http://dx.doi.org/10.3766/jaaa.15.10.2.
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This study investigated the effect of variable interstimulus intervals (ISIs) in a group of normal and ADHD (attention deficit hyperactivity disorder) adults on behavioral reaction time and the auditory P300 event-related potential. This study involved 20 adult subjects with no history of ADHD and 11 adult subjects diagnosed with ADHD. The subjects were instructed to respond to the common stimuli and ignore the rare stimulus. Significant differences in the latency of the P300a, P300b, the amplitude of the P300b, and in the number of false alarms and correct rejections between ISIs were observed in the normal group. The group with ADHD failed to show any significant differences between ISIs. Psychophysical measures of hits showed significant differences for the number of hits for ISI 2 (2 sec) between the two groups. False alarms and correct rejections for all ISIs showed significant differences between groups. Significant group differences were seen for latency of the P300a and P300b at each of the three ISIs, for amplitude of the P300a and P300b for ISI 1 and ISI 3, and for the amplitude of the P300b for ISI 2. There was a greater separation in the group with ADHD between the P300a and P300b suggesting a processing lag in that group.
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Mathis, Stéphane, Jean-Philippe Neau, Claudette Pluchon, Marie-Noëlle Fargeau, Stéphane Karolewicz, Anna Iljicsov, and Roger Gil. "Apathy in Parkinson’s Disease: An Electrophysiological Study." Neurology Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/290513.
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In Parkinson’s disease (PD), apathy (or loss of motivation) is frequent. Nevertheless, the contribution of attentional disorders to its genesis is still not clearly known. We want to determine the relation existing between apathy and attentional disorders by using P300a (or novelty P3) as a marker of the attentional process. The study included 25 patients (13 women and 12 men) with PD for whom we have determined the relationship between automatic attention (represented by P300a) and motor status, apathy, executive dysfunction, mental flexibility, inhibitory control, and depression/anxiety. We have found a correlation between the apathy score and amplitude of novelty P300 during the ON period and also a correlation of the apathy score with a decrease in amplitude of P300 during the OFF period. In a linear regression model, changes in the P300a predicted the severity of apathy independently of any other variable. We concluded firstly that the reduction in amplitude of the P300a wave was a neurophysiological marker of apathy in PD and secondly that apathy led to both dopaminergic denervation (mesolimbic) and nondopaminergic (dorsolateral prefrontal-subcortical) dysfunction.
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Weinberg, Anna, and Greg Hajcak. "The Late Positive Potential Predicts Subsequent Interference with Target Processing." Journal of Cognitive Neuroscience 23, no. 10 (October 2011): 2994–3007. http://dx.doi.org/10.1162/jocn.2011.21630.
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The current study investigated the association between neural engagement with task-irrelevant images and subsequent interference with target processing using the Emotional Interrupt paradigm [Mitchell, D., Richell, R., Leonard, A., & Blair, R. Emotion at the expense of cognition: Psychopathic individuals outperform controls on an operant response task. Journal of Abnormal Psychology, 115, 559, 2006]. Consistent with previous studies, PCA-derived factors corresponding to the early posterior negativity, P300, and late positive potential (LPP) were enhanced for emotional (i.e., both unpleasant and pleasant) compared with neutral distracters, and the P300 elicited by targets was smaller following emotional compared with neutral pictures. In addition, RTs were increased to targets that followed emotional pictures. Within-subject analyses demonstrated that slow trials were characterized by a smaller P300 and were preceded by pictures with a larger LPP. Additionally, between-subject analyses indicate that individuals with a larger LPP also demonstrated slower RTs to targets and reduced target-elicited P300s. All results were specific to the LPP and were not observed for either the early posterior negativity or the P300 elicited by task-irrelevant pictures. By relating the LPP to subsequent behavioral and ERP interference in both within- and between-subject analyses, the current study provides direct support for the notion that LPP indexes attentional engagement with visual stimuli that is uniquely associated with subsequent interference in terms of both RT slowing and P300 reduction to targets.
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Schienle, Anne, Axel Schäfer, and Ewald Naumann. "Event-Related Brain Potentials of Spider Phobics to Disorder- Relevant, Generally Disgust- and Fear-Inducing Pictures." Journal of Psychophysiology 22, no. 1 (January 2008): 5–13. http://dx.doi.org/10.1027/0269-8803.22.1.5.
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This investigation covered the disgust and fear reactivity of patients suffering from spider phobia. We analyzed event-related brain potentials and affective responses to pictures depicting spiders, as well as generally fear-inducing, disgust-inducing, and neutral content, and compared them between 18 phobic and 18 nonphobic female participants. The patients rated the spider scenes as more fear- and disgust-inducing than the controls. This was accompanied by enhanced amplitudes of the P300 and the late positive potential (LPP). The other picture types elicited comparable electrocortical and affective responses in both groups. Separate group analyses showed that the patients were characterized by larger ERP positivity (P300, LPP) for phobic than for nonphobic material. Control subjects’ P300s were equally enhanced for spider, disgust and fear pictures relative to neutral scenes. Their LPPs were smaller for spiders compared to disgust and fear. Taken altogether, motivated attention in emotional picture processing is reflected by P300 and LPP modulation.
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Dal Seno, Bernardo, Matteo Matteucci, and Luca Mainardi. "Online Detection of P300 and Error Potentials in a BCI Speller." Computational Intelligence and Neuroscience 2010 (2010): 1–5. http://dx.doi.org/10.1155/2010/307254.
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Error potentials (ErrPs), that is, alterations of the EEG traces related to the subject perception of erroneous responses, have been suggested to be an elegant way to recognize misinterpreted commands in brain-computer interface (BCI) systems. We implemented a P300-based BCI speller that uses a genetic algorithm (GA) to detect P300s, and added an automatic error-correction system (ECS) based on the single-sweep detection of ErrPs. The developed system was tested on-line on three subjects and here we report preliminary results. In two out of three subjects, the GA provided a good performance in detecting P300 (90% and 60% accuracy with 5 repetitions), and it was possible to detect ErrP with an accuracy (roughly 60%) well above the chance level. In our knowledge, this is the first time that ErrP detection is performed on-line in a P300-based BCI. Preliminary results are encouraging, but further refinements are needed to improve performances.
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Shelley-Tremblay, John F., Joshua C. Eyer, and Benjamin D. Hill. "A Laboratory Word Memory Test Analogue Differentiates Intentional Feigning from True Responding Using the P300 Event-Related Potential." Brain Sciences 9, no. 5 (May 14, 2019): 109. http://dx.doi.org/10.3390/brainsci9050109.
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Symptom exaggeration and feigned cognitive impairment occur commonly in forensic and medicolegal evaluations. As a result, methods to detect feigned cognitive impairment are an indispensable component of neuropsychological assessments. This study reports the results of two neurophysiological experiments using a forced-choice recognition task built from the stimuli of the Word Memory Test and Medical Symptom Validity Test as well as a new linguistically informed stimulus set. Participant volunteers were instructed either to do their best or to feign cognitive impairment consistent with a mild traumatic brain injury while their brain activity was monitored using event-related potentials (ERP). Experiment 1 varied instructions across individuals, whereas Experiment 2 varied instructions within individuals. The target brain component was a positive deflection indicating stimulus recognition that occurs approximately 300 ms after exposure to a stimulus (i.e., the P300). Multimodal comparison (P300 amplitude to behavioral accuracy) allowed the detection of feigned cognitive impairment. Results indicate that, for correct responses, P300s were equivalent for the simulated malingering and good effort conditions. However, for incorrect responses, feigned impairment produced reliable but significantly reduced P300 amplitudes. Although the P300 is an automatic index of recognition—even when knowledge is hidden—its amplitude appears capable of modulation by feigning strategies. Implications of this finding are discussed for research and clinical applications.
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Poizat, Coralie, Pier Lorenzo Puri, Yan Bai, and Larry Kedes. "Phosphorylation-Dependent Degradation of p300 by Doxorubicin-Activated p38 Mitogen-Activated Protein Kinase in Cardiac Cells." Molecular and Cellular Biology 25, no. 7 (April 1, 2005): 2673–87. http://dx.doi.org/10.1128/mcb.25.7.2673-2687.2005.
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ABSTRACT p300 and CBP are general transcriptional coactivators implicated in different cellular processes, including regulation of the cell cycle, differentiation, tumorigenesis, and apoptosis. Posttranslational modifications such as phosphorylation are predicted to select a specific function of p300/CBP in these processes; however, the identification of the kinases that regulate p300/CBP activity in response to individual stimuli and the physiological significance of p300 phosphorylation have not been elucidated. Here we demonstrate that the cardiotoxic anticancer agent doxorubicin (adriamycin) induces the phosphorylation of p300 in primary neonatal cardiomyocytes. Hyperphosphorylation precedes the degradation of p300 and parallels apoptosis in response to doxorubicin. Doxorubicin-activated p38 kinases α and β associate with p300 and are implicated in the phosphorylation-mediated degradation of p300, as pharmacological blockade of p38 prevents p300 degradation. p38 phosphorylates p300 in vitro at both the N and C termini of the protein, and enforced activation of p38 by the constitutively active form of its upstream kinase (MKK6EE) triggers p300 degradation. These data support the conclusion that p38 mitogen-activated protein kinase regulates p300 protein stability and function in cardiomyocytes undergoing apoptosis in response to doxorubicin.
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Bragagnolo Júnior, Maurício Augusto, Vinícius Teodoro, Lígia Mendonça Lucchesi, Ruth Ferreira Santos, Ana Cristina de Castro Amaral Feldner, Tarsila Campanha da Rocha Ribeiro, Sérgio Tufik, and Mário Kondo. "Correlação entre a amônia e o potencial evocado relacionado a eventos (P300) em pacientes cirróticos." Revista Neurociências 17, no. 2 (January 23, 2019): 122–27. http://dx.doi.org/10.34024/rnc.2009.v17.8568.
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A amônia é a neurotoxina que melhor explica alterações cognitivas em cirróticos e o potencial evocado relacionado a eventos auditivos (P300) tem sido considerado um bom método para rastreá-las. Entretanto, é ainda desconhecido se pode ele pode ser influenciado pelas concentrações de amônia. Objetivo. avaliar a correlação entre amônia arterial e o P300 em cirróticos. Método. Cirróticos sem encefalopatia hepática foram submetidos à determinação da dosagem arterial de amônia arterial, P300 e avaliação da gravidade da doença hepática. O P300 foi anormal quando a latência de P300 foi superior ao limite superior da normalidade determinado por estudo normativo. Resultados. Avaliados 48 pacientes, com P300 anormal em 36 (75%). Aqueles com P300 anormal apresentaram amônia arterial significativamente maior do que aqueles com P300 normal (197±156 vs. 90±82 mmol/L; p <0,05). Amônia ³300 mmol/L também se associou à anormalidade do P300. Conclusão. A amônia arterial foi significativamente maior em cirróticos com P300 anormal e maiores níveis se associaram à anormalidade do exame, sugerindo que o P300 é boa ferramenta para rastrear anormalidades cognitivas em cirróticos, desde que se correlaciona com a principal substância envolvida na fisiopatogenia da encefalopatia hepática. >
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Sartorelli, V., J. Huang, Y. Hamamori, and L. Kedes. "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C." Molecular and Cellular Biology 17, no. 2 (February 1997): 1010–26. http://dx.doi.org/10.1128/mcb.17.2.1010.
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By searching for molecules that assist MyoD in converting fibroblasts to muscle cells, we have found that p300 and CBP, two related molecules that act as transcriptional adapters, coactivate the myogenic basic-helix-loop-helix (bHLH) proteins. Coactivation by p300 involves novel physical interactions between p300 and the amino-terminal activation domain of MyoD. In particular, disruption of the FYD domain, a group of three amino acids conserved in the activation domains of other myogenic bHLH proteins, drastically diminishes the transactivation potential of MyoD and abolishes both p300-mediated coactivation and the physical interaction between MyoD and p300. Two domains of p300, at its amino and carboxy terminals, independently function to both mediate coactivation and physically interact with MyoD. A truncated segment of p300, unable to bind MyoD, acts as a dominant negative mutation and abrogates both myogenic conversion and transactivation by MyoD, suggesting that endogenous p300 is a required coactivator for MyoD function. The p300 dominant negative peptide forms multimers with intact p300. p300 and CBP serve as coactivators of another class of transcriptional activators critical for myogenesis, myocyte enhancer factor 2 (MEF2). In fact, transactivation mediated by the MEF2C protein is potentiated by the two coactivators, and this phenomenon is associated with the ability of p300 to interact with the MADS domain of MEF2C. Our results suggest that p300 and CBP may positively influence myogenesis by reinforcing the transcriptional autoregulatory loop established between the myogenic bHLH and the MEF2 factors.
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Gruber, Martina, Lavinia Ferrone, Martin Puhr, Frédéric R. Santer, Tobias Furlan, Iris E. Eder, Natalie Sampson, Georg Schäfer, Florian Handle, and Zoran Culig. "p300 is upregulated by docetaxel and is a target in chemoresistant prostate cancer." Endocrine-Related Cancer 27, no. 3 (March 2020): 187–98. http://dx.doi.org/10.1530/erc-19-0488.
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Administration of the microtubule inhibitor docetaxel is a common treatment for metastatic castration-resistant prostate cancer (mCRPC) and results in prolonged patient overall survival. Usually, after a short period of time chemotherapy resistance emerges and there is urgent need to find new therapeutic targets to overcome therapy resistance. The lysine-acetyltransferase p300 has been correlated to prostate cancer (PCa) progression. Here, we aimed to clarify a possible function of p300 in chemotherapy resistance and verify p300 as a target in chemoresistant PCa. Immunohistochemistry staining of tissue samples revealed significantly higher p300 protein expression in patients who received docetaxel as a neoadjuvant therapy compared to control patients. Elevated p300 expression was confirmed by analysis of publicly available patient data, where significantly higher p300 mRNA expression was found in tissue of mCRPC tumors of docetaxel-treated patients. Consistently, docetaxel-resistant PCa cells showed increased p300 protein expression compared to docetaxel-sensitive counterparts. Docetaxel treatment of PCa cells for 72 h resulted in elevated p300 expression. shRNA-mediated p300 knockdown did not alter colony formation efficiency in docetaxel-sensitive cells, but significantly reduced clonogenic potential of docetaxel-resistant cells. Downregulation of p300 in docetaxel-resistant cells also impaired cell migration and invasion. Taken together, we showed that p300 is upregulated by docetaxel, and our findings suggest that p300 is a possible co-target in treatment of chemoresistant PCa.
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Mink, S., B. Haenig, and K. H. Klempnauer. "Interaction and functional collaboration of p300 and C/EBPbeta." Molecular and Cellular Biology 17, no. 11 (November 1997): 6609–17. http://dx.doi.org/10.1128/mcb.17.11.6609.
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Transcriptional coactivators such as p300 and CREB-binding protein (CBP) function as important elements in the transcription factor network, linking individual transactivators via protein-protein interactions to the basal transcriptional machinery. We have investigated whether p300 plays a role in transactivation mediated by C/EBPbeta, a conserved member of the C/EBP family. We show that C/EBPbeta-dependent transactivation is strongly inhibited by adenovirus E1A but not by E1A mutants defective in p300 binding. Ectopic expression of p300 reverses the E1A-dependent inhibition and increases the transactivation potential of C/EBPbeta. Furthermore, we show that C/EBPbeta and p300 interact with each other and demonstrate that the sequences responsible for interaction map to the E1A binding region of p300 and the amino terminus of C/EBPbeta. Finally, we show that the minimal C/EBPbeta binding site of p300 acts as a dominant-negative inhibitor of C/EBPbeta. These observations identify p300 as a bona fide coactivator for C/EBPbeta. C/EBPbeta is highly expressed in the myelomonocytic lineage of the hematopoietic system and cooperates with Myb to activate mim-1, a gene specifically expressed during myelomonocytic differentiation. Recent evidence has shown that Myb recruits CBP (and presumably p300) as a coactivator and, in contrast to C/EBPbeta, interacts with the CREB binding site of p300-CBP. We show that p300 not only stimulates the activity of Myb and C/EBPbeta individually but also increases the synergy between them. Thus, our results reveal a novel function of p300: in addition to linking specific transcription factors to the basal transcriptional machinery, p300 also mediates the cooperation between transactivators interacting with different domains of p300.
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Yaciuk, P., and E. Moran. "Analysis with specific polyclonal antiserum indicates that the E1A-associated 300-kDa product is a stable nuclear phosphoprotein that undergoes cell cycle phase-specific modification." Molecular and Cellular Biology 11, no. 11 (November 1991): 5389–97. http://dx.doi.org/10.1128/mcb.11.11.5389-5397.1991.
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Binding of a 300-kDa host cell protein (p300) is tightly correlated with the ability of the adenovirus E1A products to induce quiescent baby rat kidney cells to proliferate. We have generated rabbit polyclonal antibodies against p300 to characterize this protein further. We have found p300 to be a nuclear phosphoprotein that is actively synthesized in both quiescent and proliferating baby rat kidney cells. In partially purified mitotic cell populations, we observe a form of p300 with decreased electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels that shares a nearly identical partial proteolytic digest pattern with p300. The slower-migrating form of p300 is greatly reduced by treating immune complexes with potato acid phosphatase. The relative stability and presence of p300 even in resting cells suggests that p300 has a basal cell function, but the appearance of differentially modified forms during the cell cycle suggests the possibility that p300 function is modulated specifically in growing cells.
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Mansor, Aida Azlina, Salmi Mohd Isa, and Syaharudin Shah Mohd Noor. "P300 and decision-making in neuromarketing." Neuroscience Research Notes 4, no. 3 (September 4, 2021): 21–26. http://dx.doi.org/10.31117/neuroscirn.v4i3.83.
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Neuromarketing provides insights into consumers' decision-making that traditional marketing test methods cannot offer. The foundation in the process of decision-making is P300. Thus, the P300 wave is a potential Event-Related Component (ERP) used to measure consumers' decision-making process. The P300 wave represents a positive transition in human event-related potential. Therefore, the P300 is determined by measuring the amplitude and latency of the consumers. A higher P300 amplitude indicates greater confidence in the decision-making process, while a longer P300 latency indicates lower attentiveness. Thus, P300 in neuroscience, which investigates customers' responses in-depth, cannot be accomplished by typical marketing methods. For many years, P300 components such as attitudes, preferences, and information-based decision-making have been examined extensively in marketing-related research. However, a review of an ERP in neuromarketing method is fewer reported. This mini review describes some analysis on P300 and decision-making by several researchers.
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Yaciuk, P., and E. Moran. "Analysis with specific polyclonal antiserum indicates that the E1A-associated 300-kDa product is a stable nuclear phosphoprotein that undergoes cell cycle phase-specific modification." Molecular and Cellular Biology 11, no. 11 (November 1991): 5389–97. http://dx.doi.org/10.1128/mcb.11.11.5389.
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Binding of a 300-kDa host cell protein (p300) is tightly correlated with the ability of the adenovirus E1A products to induce quiescent baby rat kidney cells to proliferate. We have generated rabbit polyclonal antibodies against p300 to characterize this protein further. We have found p300 to be a nuclear phosphoprotein that is actively synthesized in both quiescent and proliferating baby rat kidney cells. In partially purified mitotic cell populations, we observe a form of p300 with decreased electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels that shares a nearly identical partial proteolytic digest pattern with p300. The slower-migrating form of p300 is greatly reduced by treating immune complexes with potato acid phosphatase. The relative stability and presence of p300 even in resting cells suggests that p300 has a basal cell function, but the appearance of differentially modified forms during the cell cycle suggests the possibility that p300 function is modulated specifically in growing cells.
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Kasper, Lawryn H., Tomofusa Fukuyama, Michelle A. Biesen, Fayçal Boussouar, Caili Tong, Antoine de Pauw, Peter J. Murray, Jan M. A. van Deursen, and Paul K. Brindle. "Conditional Knockout Mice Reveal Distinct Functions for the Global Transcriptional Coactivators CBP and p300 in T-Cell Development." Molecular and Cellular Biology 26, no. 3 (February 1, 2006): 789–809. http://dx.doi.org/10.1128/mcb.26.3.789-809.2006.
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ABSTRACT The global transcriptional coactivators CREB-binding protein (CBP) and the closely related p300 interact with over 312 proteins, making them among the most heavily connected hubs in the known mammalian protein-protein interactome. It is largely uncertain, however, if these interactions are important in specific cell lineages of adult animals, as homozygous null mutations in either CBP or p300 result in early embryonic lethality in mice. Here we describe a Cre/LoxP conditional p300 null allele (p300 flox ) that allows for the temporal and tissue-specific inactivation of p300. We used mice carrying p300 flox and a CBP conditional knockout allele (CBP flox ) in conjunction with an Lck-Cre transgene to delete CBP and p300 starting at the CD4− CD8− double-negative thymocyte stage of T-cell development. Loss of either p300 or CBP led to a decrease in CD4+ CD8+ double-positive thymocytes, but an increase in the percentage of CD8+ single-positive thymocytes seen in CBP mutant mice was not observed in p300 mutants. T cells completely lacking both CBP and p300 did not develop normally and were nonexistent or very rare in the periphery, however. T cells lacking CBP or p300 had reduced tumor necrosis factor alpha gene expression in response to phorbol ester and ionophore, while signal-responsive gene expression in CBP- or p300-deficient macrophages was largely intact. Thus, CBP and p300 each supply a surprising degree of redundant coactivation capacity in T cells and macrophages, although each gene has also unique properties in thymocyte development.
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Asahara, Hiroshi, Sophie Tartare-Deckert, Takeya Nakagawa, Tsuyoshi Ikehara, Fumiko Hirose, Tony Hunter, Takashi Ito, and Marc Montminy. "Dual Roles of p300 in Chromatin Assembly and Transcriptional Activation in Cooperation with Nucleosome Assembly Protein 1 In Vitro." Molecular and Cellular Biology 22, no. 9 (May 1, 2002): 2974–83. http://dx.doi.org/10.1128/mcb.22.9.2974-2983.2002.
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ABSTRACT In a yeast two-hybrid screen to identify proteins that bind to the KIX domain of the coactivator p300, we obtained cDNAs encoding nucleosome assembly protein 1 (NAP-1), a 60-kDa histone H2A-H2B shuttling protein that promotes histone deposition. p300 associates preferentially with the H2A-H2B-bound form of NAP-1 rather than with the unbound form of NAP-1. Formation of NAP-1-p300 complexes was found to increase during S phase, suggesting a potential role for p300 in chromatin assembly. In micrococcal nuclease and supercoiling assays, addition of p300 promoted efficient chromatin assembly in vitro in conjunction with NAP-1 and ATP-utilizing chromatin assembly and remodeling factor; this effect was dependent in part on the intrinsic histone acetyltransferase activity of p300. Surprisingly, NAP-1 potently inhibited acetylation of core histones by p300, suggesting that efficient assembly requires acetylation of either NAP-1 or p300 itself. As p300 acted cooperatively with NAP-1 in stimulating transcription from a chromatin template in vitro, our results suggest a dual role of NAP-1-p300 complexes in promoting chromatin assembly and transcriptional activation.
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Chen, Jihong, Jonathan R. St-Germain, and Qiao Li. "B56 Regulatory Subunit of Protein Phosphatase 2A Mediates Valproic Acid-Induced p300 Degradation." Molecular and Cellular Biology 25, no. 2 (January 15, 2005): 525–32. http://dx.doi.org/10.1128/mcb.25.2.525-532.2005.
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ABSTRACT Transcriptional coactivator p300 is required for embryonic development and cell proliferation. Valproic acid, a histone deacetylase inhibitor, is widely used in the therapy of epilepsy and bipolar disorder. However, it has intrinsic teratogenic activity through unidentified mechanisms. We report that valproic acid stimulates proteasome-dependent p300 degradation through augmentation of gene expression of the B56γ regulatory subunits of protein phosphatase 2A. The B56γ3 regulatory and catalytic subunits of protein phosphatase 2A interact with p300. Overexpression of the B56γ3 subunit leads to proteasome-mediated p300 degradation and represses p300-dependent transcriptional activation, which requires the B56γ3 interaction domain of p300. Conversely, silencing of the B56γ subunit expression by RNA interference increases the stability and transcriptional activity of the coactivator. Our study establishes the functional interaction between protein phosphatase 2A and p300 activity and provides direct evidence for signal-dependent control of p300 function.
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Tampas, Joanna W., Ashley W. Harkrider, and Mark S. Hedrick. "Neurophysiological Indices of Speech and Nonspeech Stimulus Processing." Journal of Speech, Language, and Hearing Research 48, no. 5 (October 2005): 1147–64. http://dx.doi.org/10.1044/1092-4388(2005/081).
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Auditory event-related potentials (mismatch negativity and P300) and behavioral discrimination were measured to synthetically generated consonant-vowel (CV) speech and nonspeech contrasts in 10 young adults with normal auditory systems. Previous research has demonstrated that behavioral and P300 responses reflect a phonetic, categorical level of processing. The aims of the current investigation were (a) to examine whether the mismatch negativity (MMN) response is also influenced by the phonetic characteristics of a stimulus or if it reflects purely an acoustic level of processing and (b) to expand our understanding of the neurophysiology underlying categorical perception, a phenomenon crucial in the processing of speech. The CVs were 2 within-category stimuli and the nonspeech stimuli were 2 glides whose frequency ramps matched the formant transitions of the CV stimuli. Listeners exhibited better behavioral discrimination to the nonspeech versus speech stimuli in same/different and oddball behavioral paradigms. MMN responses were elicited by the nonspeech stimuli, but absent to CV speech stimuli. Larger amplitude and earlier P300s were elicited by the nonspeech stimuli, while smaller and longer latency P300s were elicited by the speech stimulus contrast. Results suggest that the 2 types of stimuli were processed differently when measured behaviorally, with MMN, or P300. The better discrimination and clearer neurophysiological representation of the frequency glide, nonspeech stimuli versus the CV speech stimuli of analogous acoustic content support (a) categorical perception representation at the level of the MMN generators and (b) parallel processing of acoustic (sensory) and phonetic (categorical) information at the level of the MMN generators.
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Chen, Shali, Biao Feng, Biju George, Rana Chakrabarti, Megan Chen, and Subrata Chakrabarti. "Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells." American Journal of Physiology-Endocrinology and Metabolism 298, no. 1 (January 2010): E127—E137. http://dx.doi.org/10.1152/ajpendo.00432.2009.
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Sustained hyperglycemia in diabetes causes alteration of a large number of transcription factors and mRNA transcripts, leading to tissue damage. We investigated whether p300, a transcriptional coactivator with histone acetyl transferase activity, regulates glucose-induced activation of transcription factors and subsequent upregulation of vasoactive factors and extracellular matrix (ECM) proteins in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated in varied glucose concentrations and were studied after p300 small interfering RNA (siRNA) transfection, p300 overexpression, or incubation with the p300 inhibitor curcumin. Histone H2AX phosphorylation and lysine acetylation were examined for oxidative DNA damage and p300 activation. Screening for transcription factors was performed with the Luminex system. Alterations of selected transcription factors were validated. mRNA expression of p300, endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and fibronectin (FN) and its splice variant EDB+FN and FN protein production were analyzed. HUVECs in 25 mmol/l glucose showed increased p300 production accompanied by increased binding of p300 to ET-1 and FN promoters, augmented histone acetylation, H2AX phosphorylation, activation of multiple transcription factors, and increased mRNA expression of vasoactive factors and ECM proteins. p300 overexpression showed a glucose-like effect on the mRNA expression of ET-1, VEGF, and FN. Furthermore, siRNA-mediated p300 blockade or chemical inhibitor of p300 prevented such glucose-induced changes. Similar mRNA upregulation was also seen in the organ culture of vascular tissues, which was prevented by p300 siRNA transfection. Data from these studies suggest that glucose-induced p300 upregulation is an important upstream epigenetic mechanism regulating gene expression of vasoactive factors and ECM proteins in endothelial cells and is a potential therapeutic target for diabetic complications.
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Manning, E. Tory, Tsuyoshi Ikehara, Takashi Ito, James T. Kadonaga, and W. Lee Kraus. "p300 Forms a Stable, Template-Committed Complex with Chromatin: Role for the Bromodomain." Molecular and Cellular Biology 21, no. 12 (June 15, 2001): 3876–87. http://dx.doi.org/10.1128/mcb.21.12.3876-3887.2001.
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ABSTRACT The nature of the interaction of coactivator proteins with transcriptionally active promoters in chromatin is a fundamental question in transcriptional regulation by RNA polymerase II. In this study, we used a biochemical approach to examine the functional association of the coactivator p300 with chromatin templates. Using in vitro transcription template competition assays, we observed that p300 forms a stable, template-committed complex with chromatin during the transcription process. The template commitment is dependent on the time of incubation of p300 with the chromatin template and occurs independently of the presence of a transcriptional activator protein. In studies examining interactions between p300 and chromatin, we found that p300 binds directly to chromatin and that the binding requires the p300 bromodomain, a conserved 110-amino-acid sequence found in many chromatin-associated proteins. Furthermore, we observed that the isolated p300 bromodomain binds directly to histones, preferentially to histone H3. However, the isolated p300 bromodomain does not bind to nucleosomal histones under the same assay conditions, suggesting that free histones and nucleosomal histones are not equivalent as binding substrates. Collectively, our results suggest that the stable association of p300 with chromatin is mediated, at least in part, by the bromodomain and is critically important for p300 function. Furthermore, our results suggest a model for p300 function that involves distinct activator-dependent targeting and activator-independent chromatin binding activities.
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Rocha, Caroline Nunes, Carmen Silvia Molleis Galego Miziara, Maria Luiza Giraldes de Manreza, and Eliane Schochat. "Electrophysiological and auditory behavioral evaluation of individuals with left temporal lobe epilepsy." Arquivos de Neuro-Psiquiatria 68, no. 1 (February 2010): 18–24. http://dx.doi.org/10.1590/s0004-282x2010000100005.
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The purpose of this study was to determine the repercussions of left temporal lobe epilepsy (TLE) for subjects with left mesial temporal sclerosis (LMTS) in relation to the behavioral test-Dichotic Digits Test (DDT), event-related potential (P300), and to compare the two temporal lobes in terms of P300 latency and amplitude. We studied 12 subjects with LMTS and 12 control subjects without LMTS. Relationships between P300 latency and P300 amplitude at sites C3A1,C3A2,C4A1, and C4A2, together with DDT results, were studied in inter-and intra-group analyses. On the DDT, subjects with LMTS performed poorly in comparison to controls. This difference was statistically significant for both ears. The P300 was absent in 6 individuals with LMTS. Regarding P300 latency and amplitude, as a group, LMTS subjects presented trend toward greater P300 latency and lower P300 amplitude at all positions in relation to controls, difference being statistically significant for C3A1 and C4A2. However, it was not possible to determine laterality effect of P300 between affected and unaffected hemispheres.
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Peng, Yu-Cai, David E. Breiding, Francis Sverdrup, James Richard, and Elliot J. Androphy. "AMF-1/Gps2 Binds p300 and Enhances Its Interaction with Papillomavirus E2 Proteins." Journal of Virology 74, no. 13 (July 1, 2000): 5872–79. http://dx.doi.org/10.1128/jvi.74.13.5872-5879.2000.
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ABSTRACT The cellular protein AMF-1 (Gps2) positively modulates gene expression by the papillomavirus E2 protein (D. E. Breiding et al., Mol. Cell. Biol. 17:7208–7219, 1997). We show here that AMF-1 also binds the transcriptional coactivator p300 in vitro and in vivo. E2 interacted weakly with p300. These observations led to a model in which AMF-1 recruits p300 into a complex with E2. Cotransfection of AMF-1 or p300 stimulated levels of E2-dependent transcription, while cotransfection of both AMF-1 and p300 showed an additive effect. The functional significance of p300 recruitment for E2 transactivation was evidenced by repression of E2-activated transcription by adenovirus E1A, which inhibits both coactivator and acetylase activities of p300. Antibodies to AMF-1 or E2 immunoprecipitated histone acetylase activity from cell lysates. Western blotting using antibody against acetyl-lysine failed to detect acetylation of AMF-1 or E2 in complex with p300. These results suggest that AMF-1 facilitates the recruitment of p300 and its histone acetylase activity into complexes with E2 and represents a novel mechanism of transcriptional activation.
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Waddell, Aaron R., Haojie Huang, and Daiqing Liao. "CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers." Cancers 13, no. 12 (June 8, 2021): 2872. http://dx.doi.org/10.3390/cancers13122872.
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The CREB-binding protein (CBP) and p300 are two paralogous lysine acetyltransferases (KATs) that were discovered in the 1980s–1990s. Since their discovery, CBP/p300 have emerged as important regulatory proteins due to their ability to acetylate histone and non-histone proteins to modulate transcription. Work in the last 20 years has firmly established CBP/p300 as critical regulators for nuclear hormone signaling pathways, which drive tumor growth in several cancer types. Indeed, CBP/p300 are critical co-activators for the androgen receptor (AR) and estrogen receptor (ER) signaling in prostate and breast cancer, respectively. The AR and ER are stimulated by sex hormones and function as transcription factors to regulate genes involved in cell cycle progression, metabolism, and other cellular functions that contribute to oncogenesis. Recent structural studies of the AR/p300 and ER/p300 complexes have provided critical insights into the mechanism by which p300 interacts with and activates AR- and ER-mediated transcription. Breast and prostate cancer rank the first and forth respectively in cancer diagnoses worldwide and effective treatments are urgently needed. Recent efforts have identified specific and potent CBP/p300 inhibitors that target the acetyltransferase activity and the acetytllysine-binding bromodomain (BD) of CBP/p300. These compounds inhibit AR signaling and tumor growth in prostate cancer. CBP/p300 inhibitors may also be applicable for treating breast and other hormone-dependent cancers. Here we provide an in-depth account of the critical roles of CBP/p300 in regulating the AR and ER signaling pathways and discuss the potential of CBP/p300 inhibitors for treating prostate and breast cancer.
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Felzien, Lisa K., Susan Farrell, Jonathan C. Betts, Rashid Mosavin, and Gary J. Nabel. "Specificity of Cyclin E-Cdk2, TFIIB, and E1A Interactions with a Common Domain of the p300 Coactivator." Molecular and Cellular Biology 19, no. 6 (June 1, 1999): 4241–46. http://dx.doi.org/10.1128/mcb.19.6.4241.
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ABSTRACT The p300 and CREB binding protein (CBP) transcriptional coactivators interact with a variety of transcription factors and regulate their activity. Among the interactions that have been described, the COOH-terminal region of p300 binds to cyclin E-cyclin-dependent kinase 2 (cyclin E-Cdk2) and TFIIB, as well as to the E1A gene products of adenovirus. Inhibition of Cdk activity by Cdk inhibitors, such as p21 or p27, potentiates NF-κB activity and provides a mechanism to coordinate cell cycle progression with the transcription of genes expressed during growth arrest. In this report, we analyze the specific domains of p300 required for the binding of p300 to cyclin E-Cdk2, TFIIB, and E1A and the ability of these proteins to interact with p300, alone or in combination. 12S E1A, an inhibitor of p300-dependent transcription, reduces the binding of TFIIB, but not that of cyclin E-Cdk2, to p300. In contrast, 13S E1A, a pleiotropic transcriptional activator, does not inhibit TFIIB binding to p300, although it enhances the interaction of cyclin E-Cdk2 with p300. Modification of cyclin E-Cdk2 is most likely required for association with p300 since the interaction is observed only with cyclin E-Cdk2 purified from mammalian cells. Domain swap studies show that the cyclin homology domain of TFIIB is involved in interactions with p300, although the homologous region from cyclin E does not mediate this interaction. These findings suggest that p300 or CBP function is regulated by interactions of various proteins with a common coactivator domain.
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Kadeppagari, Ravi-Kumar, Natesan Sankar, and Bayar Thimmapaya. "Adenovirus Transforming Protein E1A Induces c-Myc in Quiescent Cells by a Novel Mechanism." Journal of Virology 83, no. 10 (March 11, 2009): 4810–22. http://dx.doi.org/10.1128/jvi.02145-08.
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ABSTRACT Previously we showed that the E1A binding proteins p300 and CBP negatively regulate c-Myc in quiescent cells and that binding of E1A to p300 results in the induction of c-Myc and thereby induction of S phase. We demonstrated that p300 and HDAC3 cooperate with the transcription factor YY1 at an upstream YY1 binding site and repress the Myc promoter. Here we show that the small E1A protein induces c-Myc by interfering with the protein-protein interaction between p300, YY1, and HDAC3. Wild-type E1A but not the E1A mutants that do not bind to p300 interfered in recruitment of YY1, p300, and HDAC3 to the YY1 binding site. As E1A started to accumulate after infection, it transiently associated with promoter-bound p300. Subsequently, YY1, p300, and HDAC3 began to dissociate from the promoter. Later in infection, E1A dissociated from the promoter as well as p300, YY1, and HDAC3. Removal of HDAC3 from the promoter correlated with increased acetylation of Myc chromatin and induction. In vivo E1A stably associated with p300 and dissociated YY1 and HDAC3 from the trimolecular complex. In vitro protein-protein interaction studies indicated that E1A initially binds to the p300-YY1-HDAC3 complex, briefly associates with it, and then dissociates the complex, recapitulating somewhat the in vivo situation. Thus, E1A binding to the C-terminal region of p300 disrupts the important corepressor function provided by p300 in repressing c-Myc. Our results reveal a novel mechanism by which a viral oncoprotein activates c-Myc in quiescent cells and raise the possibility that the oncoproteins encoded by the small-DNA tumor viruses may use this mechanism to induce c-Myc, which may be critical for cell transformation.
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Houshmand Chatroudi, Amirmahmoud, Reza Rostami, Ali Motie Nasrabadi, and Yuko Yotsumoto. "Effect of inhibition indexed by auditory P300 on transmission of visual sensory information." PLOS ONE 16, no. 2 (February 22, 2021): e0247416. http://dx.doi.org/10.1371/journal.pone.0247416.
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Early electroencephalographic studies that focused on finding brain correlates of psychic events led to the discovery of the P300. Since then, the P300 has become the focus of many basic and clinical neuroscience studies. However, despite its wide applications, the underlying function of the P300 is not yet clearly understood. One line of research among the many studies that have attempted to elucidate the underlying subroutine of the P300 in the brain has suggested that the physiological function of the P300 is related to inhibition. While some intracranial, behavioral, and event-related potential studies have provided support for this theory, little is known about the inhibitory mechanism. In this study, using alpha event-related desynchronization (ERD) and effective connectivity, based on the causal (one-way directed) relationship between alpha ERD and P300 sources, we demonstrated that P300’s associated inhibition is implemented at a higher information processing stage in a localized brain region. We discuss how inhibition as the primary function of the P300 is not inconsistent with ’resource allocation’ and ’working memory updating’ theories about its cognitive function. In light of our findings regarding the scope and information processing stage of inhibition of the P300, we reconcile the inhibitory account of the P300 with working memory updating theory. Finally, based on the compensatory behavior of alpha ERD at the time of suppression of the P300, we propose two distinct yet complementary working memory mechanisms (inhibition and desynchronizing excitation) that render target perception possible.
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Labalette, Charlotte, Claire-Angélique Renard, Christine Neuveut, Marie-Annick Buendia, and Yu Wei. "Interaction and Functional Cooperation between the LIM Protein FHL2, CBP/p300, and β-Catenin." Molecular and Cellular Biology 24, no. 24 (December 15, 2004): 10689–702. http://dx.doi.org/10.1128/mcb.24.24.10689-10702.2004.
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ABSTRACT Transcriptional activation of gene expression by Wnt signaling is driven by the association of β-catenin with TCF/LEF factors and the recruitment of transcriptional coactivators. It has been shown that the LIM protein FHL2 and the acetyltransferase CBP/p300 individually stimulate β-catenin transactivating activity and that β-catenin is acetylated by p300. Here, we report that FHL2 and CBP/p300 synergistically enhanced β-catenin/TCF-mediated transcription from Wnt-responsive promoters and that the acetyltransferase activity of CBP/p300 was involved in the cooperation. CBP/p300 interacted directly with FHL2, predominantly through the CH3 domain but not the histone acetyltransferase domain, and different regions of CBP/p300 were involved in FHL2 and β-catenin binding. We provided evidence for the formation of a ternary complex by FHL2, CBP/p300, and β-catenin and for colocalization of the three proteins in the nucleus. In murine FHL2−/− embryo fibroblasts, the transactivation activity of β-catenin/TCF was markedly reduced, and this defect could be restored by exogenous expression of FHL2. However, CBP/p300 were still able to coactivate the β-catenin/TCF complex in FHL2−/− cells, suggesting that FHL2 is dispensable for the coactivator function of CBP/p300 on β-catenin. Furthermore, we found that FHL2 significantly increased acetylation of β-catenin by p300 in vivo. Finally, we showed that FHL2, CBP/p300, and β-catenin could synergistically activate androgen receptor-mediated transcription, indicating that the synergistic coactivator function is not restricted to TCF/LEF.
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Dornan, David, Harumi Shimizu, Lindsay Burch, Amanda J. Smith, and Ted R. Hupp. "The Proline Repeat Domain of p53 Binds Directly to the Transcriptional Coactivator p300 and Allosterically Controls DNA-Dependent Acetylation of p53." Molecular and Cellular Biology 23, no. 23 (December 1, 2003): 8846–61. http://dx.doi.org/10.1128/mcb.23.23.8846-8861.2003.
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ABSTRACT The transcription coactivator p300 cannot acetylate native p53 tetramers, thus revealing intrinsic conformational constraints on p300-catalyzed acetylation. Consensus site DNA is an allosteric effector that promotes acetylation of p53, suggesting that p300 has an undefined conformationally flexible interface within the p53 tetramer. To identify such conformationally responsive p300-binding sites, p300 was subjected to peptide selection from a phage-peptide display library, a technique that can define novel protein-protein interfaces. The enriched p300-binding peptides contained a proline repeat (PXXP/PXPXP) motif, and five proline repeat motifs actually reside within the p53 transactivation domain, suggesting that this region of p53 may harbor the second p300 contact site. p300 binds in vitro to PXXP-containing peptides derived from the proline repeat domain, and PXXP-containing peptides inhibit sequence-specific DNA-dependent acetylation of p53, indicating that p300 docking to both the LXXLL and contiguous PXXP motif in p53 is required for p53 acetylation. Deletion of the proline repeat motif of p53 prevents DNA-dependent acetylation of p53 by occluding p300 from the p53-DNA complex. Sequence-specific DNA places an absolute requirement for the proline repeat domain to drive p53 acetylation in vivo. Chromatin immunoprecipitation was used to show that the proline repeat deletion mutant p53 is bound to the p21 promoter in vivo, but it is not acetylated, indicating that proline-directed acetylation of p53 is a post-DNA binding event. The PXXP repeat expands the basic interface of a p300-targeted transactivation domain, and proline-directed acetylation of p53 at promoters indicates that p300-mediated acetylation can be highly constrained by substrate conformation in vivo.
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Zhang, Weiqing, John W. Nisbet, Bjorn Albrecht, Wei Ding, Fatah Kashanchi, Joshua T. Bartoe, and Michael D. Lairmore. "Human T-Lymphotropic Virus Type 1 p30IIRegulates Gene Transcription by Binding CREB Binding Protein/p300." Journal of Virology 75, no. 20 (October 15, 2001): 9885–95. http://dx.doi.org/10.1128/jvi.75.20.9885-9895.2001.
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ABSTRACT The highly conserved coadapters CREB binding protein (CBP) and p300 form complexes with CREB as well as other DNA binding transcription factors to modulate chromatin remodeling and thus transcription. Human T-lymphotropic virus type 1 (HTLV-1) transcription is controlled, in part, by the CREB/ATF family of transcription factors which bind promoter sequences and function as complexes with the viral oncogenic protein Tax. We have reported that the nuclear localizing protein p30II of HTLV-1 functions as a transcription factor, differentially modulates CREB-responsive promoters, and is critical for maintenance of proviral loads in rabbits. In this study, we tested whether p30IIdirectly interacts with CBP/p300 to modulate gene transcription. Gal4(BD)-p30II-mediated transactivation was enhanced following exogenous expression of p300 and was competitively repressed by the p300 binding protein, adenovirus E1A, and E1ACR2 (mutated for retinoblastoma binding but retaining p300 binding). In contrast, E1ACR1 (mutated for p300 binding) failed to alter Gal4(BD)-p30II-mediated transactivation. In addition, Gal4(BD)-p30II-mediated transactivation was competitively inhibited by the cotransfection of CMV-p30II-HA and CMV-Tax but could be rescued by exogenous p300. Importantly, we demonstrate that p30II colocalizes with p300 in cell nuclei and directly binds to CBP/p300 in cells. Deletion mutants of CBP/p300 were used to localize the site critical for binding p30II to a highly conserved KIX region. DNA binding assays confirmed the interference of p30II with the assembly of CREB-Tax-p300/CBP multiprotein complexes on 21-bp repeat oligonucleotides in vitro. Collectively, our results demonstrate that CBP/p300 is a cellular protein target for HTLV-1 p30II and mediates its transcriptional effects in vivo.
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Chakraborty, Raja, Allison C. Ostriker, Yi Xie, Jui M. Dave, Ana Gamez-Mendez, Payel Chatterjee, Yaw Abu, et al. "Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity." Circulation 145, no. 23 (June 7, 2022): 1720–37. http://dx.doi.org/10.1161/circulationaha.121.057599.
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Background: Vascular smooth muscle cell (VSMC) phenotypic switching contributes to cardiovascular diseases. Epigenetic regulation is emerging as a key regulatory mechanism, with the methylcytosine dioxygenase TET2 acting as a master regulator of smooth muscle cell phenotype. The histone acetyl-transferases p300 and CREB-binding protein (CBP) are highly homologous and often considered to be interchangeable, and their roles in smooth muscle cell phenotypic regulation are not known. Methods: We assessed the roles of p300 and CBP in human VSMC with knockdown, in inducible smooth muscle–specific knockout mice (inducible knockout [iKO]; p300 iKO or CBP iKO ), and in samples of human intimal hyperplasia. Results: P300, CBP, and histone acetylation were differently regulated in VSMCs undergoing phenotypic switching and in vessel remodeling after vascular injury. Medial p300 expression and activity were repressed by injury, but CBP and histone acetylation were induced in neointima. Knockdown experiments revealed opposing effects of p300 and CBP in the VSMC phenotype: p300 promoted contractile protein expression and inhibited migration, but CBP inhibited contractile genes and enhanced migration. p300 iKO mice exhibited severe intimal hyperplasia after arterial injury compared with controls, whereas CBP iKO mice were entirely protected. In normal aorta, p300 iKO reduced, but CBP iKO enhanced, contractile protein expression and contractility compared with controls. Mechanistically, we found that these histone acetyl-transferases oppositely regulate histone acetylation, DNA hydroxymethylation, and PolII (RNA polymerase II) binding to promoters of differentiation-specific contractile genes. Our data indicate that p300 and TET2 function together, because p300 was required for TET2-dependent hydroxymethylation of contractile promoters, and TET2 was required for p300-dependent acetylation of these loci. TET2 coimmunoprecipitated with p300, and this interaction was enhanced by rapamycin but repressed by platelet-derived growth factor (PDGF) treatment, with p300 promoting TET2 protein stability. CBP did not associate with TET2, but instead facilitated recruitment of histone deacetylases (HDAC2, HDAC5) to contractile protein promoters. Furthermore, CBP inhibited TET2 mRNA levels. Immunostaining of cardiac allograft vasculopathy samples revealed that p300 expression is repressed but CBP is induced in human intimal hyperplasia. Conclusions: This work reveals that p300 and CBP serve nonredundant and opposing functions in VSMC phenotypic switching and coordinately regulate chromatin modifications through distinct functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.
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Alvarado-González, Montserrat, Edgar Garduño, Ernesto Bribiesca, Oscar Yáñez-Suárez, and Verónica Medina-Bañuelos. "P300 Detection Based on EEG Shape Features." Computational and Mathematical Methods in Medicine 2016 (2016): 1–14. http://dx.doi.org/10.1155/2016/2029791.
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We present a novel approach to describe a P300 by a shape-feature vector, which offers several advantages over the feature vector used by the BCI2000 system. Additionally, we present a calibration algorithm that reduces the dimensionality of the shape-feature vector, the number of trials, and the electrodes needed by a Brain Computer Interface to accurately detect P300s; we also define a method to find a template that best represents, for a given electrode, the subject’s P300 based on his/her own acquired signals. Our experiments with 21 subjects showed that the SWLDA’s performance using our shape-feature vector was93%, that is,10%higher than the one obtained with BCI2000-feature’s vector. The shape-feature vector is 34-dimensional for every electrode; however, it is possible to significantly reduce its dimensionality while keeping a high sensitivity. The validation of the calibration algorithm showed an averaged area under the ROC (AUROC) curve of0.88. Also, most of the subjects needed less than15trials to have an AUROC superior to0.8. Finally, we found that the electrode C4 also leads to better classification.
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Borger, Darrell R., and James A. DeCaprio. "Targeting of p300/CREB Binding Protein Coactivators by Simian Virus 40 Is Mediated through p53." Journal of Virology 80, no. 9 (May 1, 2006): 4292–303. http://dx.doi.org/10.1128/jvi.80.9.4292-4303.2006.
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ABSTRACT The primary transforming functions of simian virus 40 large T antigen (SV40 LT) are conferred primarily through the binding and inactivation of p53 and the retinoblastoma family members. Normal p53 function requires an association with the CREB binding protein (CBP)/p300 coactivators, and a ternary complex containing SV40 LT, p53, and CBP/p300 has been identified previously. In this report, we have evaluated a secondary function of p53 bound to the SV40 LT complex in mediating the binding of human CBP/p300. We demonstrate that p53 associated with SV40 LT was posttranslationally modified in a manner consistent with the binding of CBP/p300. Furthermore, expression of SV40 LT induced the proportion of p53 phosphorylated on S15. An essential function for p53 in bridging the interaction between SV40 LT and CBP/p300 was identified through the reconstitution of the SV40 LT-CBP/p300 complex upon p53 reexpression in p53-null cells. In addition, the SV40 LT-CBP/p300 complex was disrupted through RNA interference-mediated depletion of endogenous p53. We also demonstrate that SV40 LT was acetylated in a p300- and p53-dependent manner, at least in part through the CH3 domain of p300. Therefore, the binding of p53 serves to modify SV40 LT by targeting CBP and p300 binding to direct the acetylation of SV40 LT.
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He, Ti, Zhihong Yu, Hyoung Kwon, Clifford A. Toleman, Jeffrey Kudlow, and Zhixin Zhang. "Histone acetyltransferase p300 acts as a potent transcriptional co-activator for Pax5 (35.29)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S7. http://dx.doi.org/10.4049/jimmunol.178.supp.35.29.
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Abstract Pax5/BSAP is an essential regulator for B lineage cell development and function. Pax5 activates the transcription of many B lineage specific genes, such as Cd19, Mb-1 and Blnk; controls the B lineage specific IgH VH→DJH recombination and meantime, represses the expression of other lineage inappropriate genes, such as Notch1, M-csfr, G-csfr, and Ccl3, to restrict B lineage cell development. It becomes important to understand how the Pax5 activity is regulated to exert these different functions. Here, we show that co-expression of histone acetyltransferase p300 dramatically enhances Pax5-mediated activation of a Pax5 responsive luciferase reporter construct. The p300-mediated enhancement is dependent on the intrinsic histone acetyltransferase activity of p300 and the activation domain of Pax5. Pax5 interacts with p300 in vitro and forms a complex with p300 in B lineage cells. Recombinant full length p300 purified from baculovirus or 293 cells directly acetylates purified Pax5 in vitro and overexpression of p300 induces Pax5 acetylation in 293 cells. Mass spectroscopy-based analysis identified that multiple lysine residues within the Pax5 DNA binding domain were acetylated upon coexpression of p300. Mutations of lysine 67, 87, 89, 103, and 142 residues on Pax5 attenuate p300-mediated enhancement. These results suggest that p300 acts as a potent co-activator for Pax5-mediated transcription function through acetylation of the Pax5 DNA binding domain.
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Lee, J. S., R. H. See, T. Deng, and Y. Shi. "Adenovirus E1A downregulates cJun- and JunB-mediated transcription by targeting their coactivator p300." Molecular and Cellular Biology 16, no. 8 (August 1996): 4312–26. http://dx.doi.org/10.1128/mcb.16.8.4312.
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Transcription factors and cofactors play critical roles in cell growth and differentiation. Alterations of their activities either through genetic mutations or by viral oncoproteins often result in aberrant cell growth and tumorigenesis. The transcriptional cofactor p300 has recently been shown to be complexed with transcription factors YY1 and CREB. Adenovirus E1A oncoproteins target these transcription complexes via physical interactions with p300, resulting in alterations of transcription mediated by these transcription factors. Here we show that p300 is also critical for repression by E1A of the activities of cJun and JunB, two members of the AP-1 transcriptional complexes. This repressive effect of E1A is dependent on the p300-binding domain of E1A and can be relieved by overexpression of p300. These results suggest that p300 serves as a mediator protein for downregulation of AP-1 activity by E1A. This hypothesis was further supported by the following observations: (i) in the absence of E1A, overexpression of p300 stimulated transcription both through an AP-1 site present in the collagenase promoter and through Jun proteins in GAL4 fusion protein-based assays; and (ii) overexpression of a mutant p300 lacking the E1A-interacting domain reduced the responsiveness of Jun-dependent transcription to E1A repression. As predicted from the functional results, p300 physically interacted with the Jun proteins. These findings thus established that p300 is a cofactor for cJun and JunB. We propose that p300 is a common mediator protein through which E1A gains control over multiple transcriptional regulatory pathways in the host cells.
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Rikitake, Y., and E. Moran. "DNA-binding properties of the E1A-associated 300-kilodalton protein." Molecular and Cellular Biology 12, no. 6 (June 1992): 2826–36. http://dx.doi.org/10.1128/mcb.12.6.2826-2836.1992.
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One of the major E1A-associated cellular proteins is a 300-kDa product (p300) that binds to the N-terminal region of the E1A products. The p300 binding site is distinct from sequences involved in binding the retinoblastoma product and other E1A-associated cellular products such as p60-cyclin A and p107. p300 binding to E1A is linked genetically to the enhancer repression function of E1A and the other E1A-mediated gene-regulating functions as well as to the transforming functions of E1A. However, the biochemical properties of p300 have not yet been characterized. We report here that p300 has an intrinsic DNA-binding activity and shows a preferential affinity for specific DNA sequences. The sequences selectively bound by p300 are related to those of a series of enhancer elements that are recognized by NF-kappa B. The direct physical interaction of p300 with enhancer elements provides a biochemical basis for the genetic evidence linking the E1A-mediated enhancer repression function with the p300-binding activity of E1A.
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Rikitake, Y., and E. Moran. "DNA-binding properties of the E1A-associated 300-kilodalton protein." Molecular and Cellular Biology 12, no. 6 (June 1992): 2826–36. http://dx.doi.org/10.1128/mcb.12.6.2826.
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One of the major E1A-associated cellular proteins is a 300-kDa product (p300) that binds to the N-terminal region of the E1A products. The p300 binding site is distinct from sequences involved in binding the retinoblastoma product and other E1A-associated cellular products such as p60-cyclin A and p107. p300 binding to E1A is linked genetically to the enhancer repression function of E1A and the other E1A-mediated gene-regulating functions as well as to the transforming functions of E1A. However, the biochemical properties of p300 have not yet been characterized. We report here that p300 has an intrinsic DNA-binding activity and shows a preferential affinity for specific DNA sequences. The sequences selectively bound by p300 are related to those of a series of enhancer elements that are recognized by NF-kappa B. The direct physical interaction of p300 with enhancer elements provides a biochemical basis for the genetic evidence linking the E1A-mediated enhancer repression function with the p300-binding activity of E1A.
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Kimbrel, Erin A., Madeleine E. Lemieux, Xiaobo Xia, Tina N. Davis, Vivienne I. Rebel, and Andrew L. Kung. "Systematic in vivo structure-function analysis of p300 in hematopoiesis." Blood 114, no. 23 (November 26, 2009): 4804–12. http://dx.doi.org/10.1182/blood-2009-04-217794.
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Abstract Cyclic adenosine monophosphate response element binding (CREB)–binding protein (CBP) and p300 are multidomain transcriptional coactivators that help assemble large regulatory complexes at sites of active transcription. Nullizygosity of CBP or p300 results in pervasive defects in hematopoiesis. To systematically assess the structural domains of p300 required for normal hematopoiesis, we used recombinase-mediated cassette exchange to create an allelic series of coisogenic embryonic stem cells, each expressing a different mutant of p300 from the endogenous locus. We found that deletion of either the KIX or CH1 domain caused profound and pervasive defects in hematopoiesis, whereas the loss of most other domains had only lineage-restricted effects. When expressed from the p300 locus, an extra copy of CBP largely compensated for a lack of p300. Surprisingly, mutation of the p300 histone acetyltransferase (HAT) domain had minimal effects on hematopoiesis, and actually increased progenitor and stem cell numbers and proliferative potential. Our results suggest that, in distinct contrast to other organ systems, HAT activity does not provide a critical function for hematopoietic development and emphasizes the importance of enzyme-independent functions of p300.
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Namwanje, Maria, Longhua Liu, Michelle Chan, Nikki Aaron, Michael J. Kraakman, and Li Qiang. "The depot-specific and essential roles of CBP/p300 in regulating adipose plasticity." Journal of Endocrinology 240, no. 2 (February 2019): 257–69. http://dx.doi.org/10.1530/joe-18-0361.
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Fat remodeling has been extensively explored through protein deacetylation, but not yet acetylation, as a viable therapeutic approach in the management of obesity and related metabolic disorders. Here, we investigated the functions of key acetyltransferases CBP/p300 in adipose remodeling and their physiological effects by generating adipose-specific deletion of CBP (Cbp-AKO), p300 (p300-AKO) and double-knockout (Cbp/p300-AKO) models. We demonstrated that Cbp-AKO exhibited marked brown remodeling of inguinal WAT (iWAT) but not epididymal WAT (eWAT) after cold exposure and that this pattern was exaggerated in diet-induced obesity (DIO). Despite this striking browning phenotype, loss of Cbp was insufficient to impact body weight or glucose tolerance. In contrast, ablation of p300 in adipose tissues had minimal effects on fat remodeling and adiposity. Surprisingly, double-knockout mice (Cbp/p300-AKO) developed severe lipodystrophy along with marked hepatic steatosis, hyperglycemia and hyperlipidemia. Furthermore, we demonstrated that pharmacological inhibition of Cbp and p300 activity suppressed adipogenesis. Collectively, these data suggest that (i) CBP, but not p300, has distinct functions in regulating fat remodeling and that this occurs in a depot-selective manner; (ii) brown remodeling occurs independently of the improvements in glucose metabolism and obesity and (iii) the combined roles of CBP and p300 are indispensable for normal adipose development.
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Shikama, Noriko, Ho Man Chan, Marija Krstic-Demonacos, Linda Smith, Chang-Woo Lee, William Cairns, and Nicholas B. La Thangue. "Functional Interaction between Nucleosome Assembly Proteins and p300/CREB-Binding Protein Family Coactivators." Molecular and Cellular Biology 20, no. 23 (December 1, 2000): 8933–43. http://dx.doi.org/10.1128/mcb.20.23.8933-8943.2000.
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ABSTRACT The p300/CREB-binding protein (CBP) family of proteins consists of coactivators that influence the activity of a wide variety of transcription factors. Although the mechanisms that allow p300/CBP proteins to achieve transcriptional control are not clear, it is believed that the regulation of chromatin is an important aspect of the process. Here, we describe a new level of p300-dependent control mediated through the functional interaction between p300/CBP and members of the family of nucleosome assembly proteins (NAP), which includes NAP1, NAP2, and TAF1. We find that NAP proteins, which have previously been implicated in the regulation of transcription factor binding to chromatin, augment the activity of different p300 targets, including p53 and E2F, through a process that is likely to involve the physical interaction between p300 and NAP. NAP proteins can form oligomers, and the results show that NAP proteins can bind to both core histones and p300 coactivator proteins, perhaps in a multicomponent ternary complex. We also provide data in support of the idea that histones can influence the interaction between p300 and NAP protein. These results argue that NAP is a functionally important component of the p300 coactivator complex and suggest that NAP may serve as a point of integration between transcriptional coactivators and chromatin.
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Deng, Wu-Guo, Ying Zhu, and Kenneth K. Wu. "Role of p300 and PCAF in regulating cyclooxygenase-2 promoter activation by inflammatory mediators." Blood 103, no. 6 (March 15, 2004): 2135–42. http://dx.doi.org/10.1182/blood-2003-09-3131.
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Abstract Coactivators p300 and CREB (cyclic adenosine monophosphate [cAMP]–response element binding protein)–binding protein (CBP) serve as an integrator for gene transcription. Their relative involvement in regulating cyclooxygenase-2 (COX-2) promoter activity had not been characterized. Using fibroblast and macrophage COX-2 transcription as a model, we determined p300 and CBP levels in nuclear extracts and their binding to a COX-2 promoter probe. CBP level was barely detectable and there was little CBP binding. In contrast, p300 was detectable in nucleus and its binding to a COX-2 promoter probe was enhanced by phorbol 12-myristate 13-acetate (PMA), interleukin-1β (IL-1β), or lipopolysaccharide (LPS). Binding of p300/CBP-associated factor (PCAF) was also up-regulated. COX-2 proteins and promoter activities induced by these agonists were augmented by p300 overexpression. Early region 1A (E1A), but not its deletion mutant, abrogated COX-2 expression induced by inflammatory mediators and with or without p300 overexpression. Molecular analysis of p300 revealed the requirement of multiple domains, including histone acetyltransferase (HAT) for COX-2 transactivation. Furthermore, roscovitine, an indirect inhibitor of p300 HAT, and histone deacetylase-1 transfection completely abolished COX-2 promoter activity. We conclude that p300 is the predominant coactivator that is essential for COX-2 transcriptional activation by proinflammatory mediators.
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Müller, Andreas, Andreas Ritzkowsky, and Gertrud Steger. "Cooperative Activation of Human Papillomavirus Type 8 Gene Expression by the E2 Protein and the Cellular Coactivator p300." Journal of Virology 76, no. 21 (November 1, 2002): 11042–53. http://dx.doi.org/10.1128/jvi.76.21.11042-11053.2002.
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ABSTRACT The E2 proteins of papillomaviruses (PV) bind to the coactivator CBP/p300 as do many other transcription factors, but the precise role of CBP/p300 in E2-specific functions is not yet understood. We show that the E2 protein of human PV type 8 (HPV8) directly binds to p300. Activation of HPV8 gene expression by low amounts of HPV8 E2 was stimulated up to sevenfold by coexpression of p300. The interaction between E2 and p300 may play a role in differentiation-dependent activation of PV gene expression, since we can show that the expression level of p300 increases during keratinocyte differentiation. Surprisingly, sequence-specific binding of E2 to its recognition sites within the regulatory region of HPV8 is not necessary for this cooperation, indicating that E2 can be recruited to the promoter via protein-protein interaction. HPV8 E2 binds via its N-terminal activation domain (AD), its C-terminal DNA binding domain (DBD), and its internal hinge region to p300 in vitro. Transient-transfection assays revealed that the AD is necessary and sufficient for cooperative activation with p300. However, we provide evidence that the interaction of the hinge and the DBD of HPV8 E2 with p300 may contribute. Our data suggest an important role of p300 in regulation of HPV8 gene expression and reveal a new mechanism by which E2 may be recruited to a promoter to activate transcription without sequence specific DNA binding.
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Zeng, Qingmei, Kun Wang, Yongxiang Zhao, Qingzhi Ma, Zhinan Chen, and Wan Huang. "Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification." Biomolecules 13, no. 3 (February 22, 2023): 417. http://dx.doi.org/10.3390/biom13030417.
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p300 acts as a transcription coactivator and an acetyltransferase that plays an important role in tumourigenesis and progression. In previous studies, it has been confirmed that p300 is an important regulator in regulating the evolution of malignant tumours and it also has extensive functions. From the perspective of non-posttranslational modification, it has been proven that p300 can participate in regulating many pathophysiological processes, such as activating oncogene transcription, promoting tumour cell growth, inducing apoptosis, regulating immune function and affecting embryo development. In recent years, p300 has been found to act as an acetyltransferase that catalyses a variety of protein modification types, such as acetylation, propanylation, butyylation, 2-hydroxyisobutyration, and lactylation. Under the catalysis of this acetyltransferase, it plays its crucial tumourigenic driving role in many malignant tumours. Therefore, the function of p300 acetyltransferase has gradually become a research hotspot. From a posttranslational modification perspective, p300 is involved in the activation of multiple transcription factors and additional processes that promote malignant biological behaviours, such as tumour cell proliferation, migration, and invasion, as well as tumour cell apoptosis, drug resistance, and metabolism. Inhibitors of p300 have been developed and are expected to become novel anticancer drugs for several malignancies. We review the characteristics of the p300 protein and its functional role in tumour from the posttranslational modification perspective, as well as the current status of p300-related inhibitor research, with a view to gaining a comprehensive understanding of p300.
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Kutas, Marta, Steven A. Hillyard, Bruce T. Volpe, and Michael S. Gazzaniga. "Late Positive Event-Related Potentials after Commissural Section in Humans." Journal of Cognitive Neuroscience 2, no. 3 (July 1990): 258–71. http://dx.doi.org/10.1162/jocn.1990.2.3.258.
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The lateral distribution of the P300 component of the event-related brain potential (ERP) was studied in five epileptic patients whose corpus callosum had been surgically sectioned and in seven neurologically intact controls. The P300 was elicited in an auditory “oddball” task using high- and low-pitched tones and in a visual oddball task in which target words were presented either to the left or right visual fields, or to both fields simultaneously. Commissurotomy altered the normal pattern of bilaterally symmetrical P300 waves over the left and right hemispheres, but in a different manner for auditory and visual stimuli. The auditory P3 to binaural tones was larger in amplitude over the right than the left hemisphere for the patients. In the visual task, the laterality of the P300 varied with the visual field of the target presentation. Left field targets elicited much larger P300 amplitudes over the right than the left hemisphere, as did bilateral targets. In contrast, right field targets triggered P300 waves of about the same amplitude over the two hemispheres. The overall amplitude of the P300 to simultaneous bilateral targets was less than the sum of the individual P300 amplitudes produced in response to the unilateral right and left field targets. These shifts in P300 laterality argue against the view that the P300 is an index of diffuse arousal or activation that is triggered in both hemispheres simultaneously irrespective of which hemisphere processes the target information. The results further demonstrate that the P300 does not depend for its production on interhemispheric comparisons of information mediated by the corpus callosum, as suggested recently by Knight et al. (1989).
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LUBMAN, DAN I., NICHOLAS B. ALLEN, LESLEY A. PETERS, and J. F. WILLIAM DEAKIN. "Electrophysiological evidence of the motivational salience of drug cues in opiate addiction." Psychological Medicine 37, no. 8 (February 5, 2007): 1203–9. http://dx.doi.org/10.1017/s0033291707009932.
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ABSTRACTBackgroundDrug-related stimuli reliably induce craving in experimental paradigms, yet are rarely cited by drug users as major precipitants of relapse. We examined the motivational significance of drug cues in opiate dependence, by exploring their impact on central attentional processes.MethodFourteen methadone-maintained subjects and 14 matched controls were studied. Subjects performed a novel active visual oddball task, consisting of opiate-related and matched neutral pictures, some of which (the oddballs) included a white cup. Subjects were fitted with a 32-channel electrode cap. The P300 for each stimulus category was identified using temporal principal components analysis.ResultsThe P300 elicited by opiate stimuli was significantly larger than that elicited by neutral stimuli in the methadone-maintained group but not in the controls. There was also a non-significant trend for the opiate stimuli to elicit larger P300s than the oddball stimuli in the addicted group.ConclusionsThese results suggest that drug cues acquire motivational salience and automatically capture attentional resources in opiate addicts, even when engaged in a non-drug-related task. Enhanced P300s to drug cues may provide an important biological marker of crucial psychological mechanisms relevant to addiction.
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Ida, Kohmei, Issay Kitabayashi, Tomohiko Taki, Masafumi Taniwaki, Keiko Noro, Masao Yamamoto, Misao Ohki, and Yasuhide Hayashi. "Adenoviral E1A-Associated Protein p300 Is Involved in Acute Myeloid Leukemia With t(11; 22)(q23; q13)." Blood 90, no. 12 (December 15, 1997): 4699–704. http://dx.doi.org/10.1182/blood.v90.12.4699.
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Abstract p300, which was originally cloned as a nuclear binding target of the adenovirus E1A oncoprotein, forms a family with cyclic-AMP response element binding protein (CREB)-binding protein (CBP). p300/CBP are considered to be transcriptional coactivators that connect the basal transcriptional machinery to various DNA-binding transcriptional factors. p300/CBP are implicated in both cell differentiation and regulation of cell-cycle. We identify here that the p300 gene is fused to the MLL gene and that in-frame MLL-p300 fusion protein is generated in acute myeloid leukemia (AML) with t(11; 22)(q23; q13). These findings suggest that the basis for the leukemogenesis of t(11; 22)-AML is the inability of p300 to regulate cell-cycle and cell differentiation after fusion with MLL.
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Ida, Kohmei, Issay Kitabayashi, Tomohiko Taki, Masafumi Taniwaki, Keiko Noro, Masao Yamamoto, Misao Ohki, and Yasuhide Hayashi. "Adenoviral E1A-Associated Protein p300 Is Involved in Acute Myeloid Leukemia With t(11; 22)(q23; q13)." Blood 90, no. 12 (December 15, 1997): 4699–704. http://dx.doi.org/10.1182/blood.v90.12.4699.4699_4699_4704.
Full textAbstract:
p300, which was originally cloned as a nuclear binding target of the adenovirus E1A oncoprotein, forms a family with cyclic-AMP response element binding protein (CREB)-binding protein (CBP). p300/CBP are considered to be transcriptional coactivators that connect the basal transcriptional machinery to various DNA-binding transcriptional factors. p300/CBP are implicated in both cell differentiation and regulation of cell-cycle. We identify here that the p300 gene is fused to the MLL gene and that in-frame MLL-p300 fusion protein is generated in acute myeloid leukemia (AML) with t(11; 22)(q23; q13). These findings suggest that the basis for the leukemogenesis of t(11; 22)-AML is the inability of p300 to regulate cell-cycle and cell differentiation after fusion with MLL.
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Mathalon, Daniel H., and Judith M. Ford. "The Long and the Short of It: Influence of Interstimulus Interval on Auditory P300 Abnormalities in Schizophrenia." Clinical Electroencephalography 33, no. 3 (July 2002): 125–35. http://dx.doi.org/10.1177/155005940203300309.
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Event-related brain potentials were recorded from 10 patients with DSM-IV schizophrenia (9 men) and 10 healthy control subjects (9 men) during the performance of two auditory oddball tasks, one using a 1.5 second interstimulus interval (ISI), the other using an 8 second ISI. P300 amplitude to target tones (.20 probability) and standard tones (.80 probability) were measured from midline electrodes Fz, Cz, and Pz. Results showed different effects of ISI in the two groups. Controls showed a slight decrease in P300 amplitude to targets but a marked increase in P300 to standards with the increase in ISI. In contrast, schizophrenic patients showed no change in the P300 to targets and a relatively small increase in P300 to standards with the ISI increase. Moreover, relative to the controls, P300 amplitude to targets was reduced in the schizophrenic patients at the short but not the long ISI. Implications for the cognitive significance of the P300 and its reduction in schizophrenia are discussed.
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Chen, Wei-Yi, Li-Jung Juan, and Bon-chu Chung. "SF-1 (Nuclear Receptor 5A1) Activity Is Activated by Cyclic AMP via p300-Mediated Recruitment to Active Foci, Acetylation, and Increased DNA Binding." Molecular and Cellular Biology 25, no. 23 (December 1, 2005): 10442–53. http://dx.doi.org/10.1128/mcb.25.23.10442-10453.2005.
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ABSTRACT Steroidogenic factor 1 (SF-1) is a nuclear receptor essential for steroidogenic gene expression, but how its activity is regulated is unclear. Here we demonstrate that p300 plays an important role in regulating SF-1 function. SF-1 was acetylated in vitro and in vivo by p300 at the KQQKK motif in the Ftz-F1 (Fushi-tarazu factor 1) box adjacent to its DNA-binding domain. Mutation of the KQQKK motif reduced the DNA-binding activity and p300-dependent activation of SF-1. When stimulated with cyclic AMP (cAMP), adrenocortical Y1 cells expressed more p300, leading to additional SF-1 association with p300 and increased SF-1 acetylation and DNA binding. It also increased SF-1 colocalization with p300 in nuclear foci. Collectively, these results indicate that SF-1 transcriptional activity is regulated by p300 in response to the cAMP signaling pathway by way of increased acetylation, DNA binding, and recruitment to nuclear foci.
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Kaida, Atsushi, Yasuo Ariumi, Keiko Baba, Masami Matsubae, Toshifumi Takao, and Kunitada Shimotohno. "Identification of a novel p300-specific-associating protein, PRS1 (phosphoribosylpyrophosphate synthetase subunit 1)." Biochemical Journal 391, no. 2 (October 10, 2005): 239–47. http://dx.doi.org/10.1042/bj20041308.
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CBP [CREB (cAMP-response-element-binding protein)-binding protein] and p300 play critical roles in transcriptional co-activation, cell differentiation, proliferation and apoptosis. Multiple transcription factors associate with CBP/p300. With the exception of the SYT oncoprotein, no proteins have been identified that specifically associate with p300, but not CBP. In the present study, we isolated a novel p300-associated protein for which no interaction with CBP was observed by GST (glutathione S-transferase) pull-down assay using Jurkat cell lysates metabolically labelled with [35S]methionine. This protein bound the KIX (kinase-inducible) domain of p300. Following resolution by two-dimensional acrylamide gel electrophoresis, we identified the KIX-domain-bound protein by MS analysis as PRS1 (phosphoribosylpyrophosphate synthetase subunit 1), a protein essential for nucleoside biosynthesis. This is the first report to demonstrate the existence of a p300 KIX-domain-specific-interacting protein that does not interact with CBP. Thus p300 may play a role in the regulation of DNA synthesis through interactions with PRS1.
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Sánchez-Molina, Sara, José Luis Oliva, Susana García-Vargas, Ester Valls, José M. Rojas, and Marian A. Martínez-Balbás. "The histone acetyltransferases CBP/p300 are degraded in NIH 3T3 cells by activation of Ras signalling pathway." Biochemical Journal 398, no. 2 (August 15, 2006): 215–24. http://dx.doi.org/10.1042/bj20060052.
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The CBP [CREB (cAMP-response-element-binding protein)-binding protein]/p300 acetyltransferases function as transcriptional co-activators and play critical roles in cell differentiation and proliferation. Accumulating evidence shows that alterations of the CBP/p300 protein levels are linked to human tumours. In the present study, we show that the levels of the CBP/p300 co-activators are decreased dramatically by continuous PDGF (platelet-derived growth factor) and Ras signalling pathway activation in NIH 3T3 fibroblasts. This effect occurs by reducing the expression levels of the CBP/p300 genes. In addition, CBP and p300 are degraded by the 26 S proteasome pathway leading to an overall decrease in the levels of the CBP/p300 proteins. Furthermore, we provide evidence that Mdm2 (murine double minute 2), in the presence of active H-Ras or N-Ras, induces CBP/p300 degradation in NIH 3T3 cells. These findings support a novel mechanism for modulating other signalling transduction pathways that require these common co-activators.