Academic literature on the topic 'Protein P300 - Transcriptional Co-activator'
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Journal articles on the topic "Protein P300 - Transcriptional Co-activator"
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Stallcup, M. R., D. Chen, S. S. Koh, H. Ma, Y. H. Lee, H. Li, B. T. Schurter, and D. W. Aswad. "Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation." Biochemical Society Transactions 28, no. 4 (August 1, 2000): 415–18. http://dx.doi.org/10.1042/bst0280415.
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Nuclear hormone receptors (NRs) activate transcription by binding to specific enhancer elements associated with target genes. Transcriptional activation is accomplished with the help of complexes of co-activator proteins that bind to NRs. p160 co-activators, a family of three related 160 kDa proteins, serve as primary co-activators by binding directly to NRs and recruiting additional secondary co-activators. Some of these (CBP/p300 and p/CAF) can acetylate histones and other proteins in the transcription complex, thus helping to modify chromatin structure and form an active transcription initiation complex. We recently discovered co-activator-associated arginine methyltransferase 1 (CARM1), which binds to p160 co-activators and thereby enhances transcriptional activation by NRs on transiently transfected reporter genes. CARM1 also methylates specific arginine residues in the N-terminal tail of histone H3 in vitro. A related arginine-specific protein methyltransferase, PRMT1, also binds p160 co-activators and enhances NR function. PRMT1 methylates histone H4 in vitro. The enhancement of NR function by CARM1, PRMT1 and p300 depends on their interactions with p160 co-activators. In the presence of p160 co-activators, some pairs of these three secondary co-activators provide a highly synergistic enhancement of NR function on transiently transfected reporter genes. We have also observed an enhancement of NR function on stably integrated reporter genes by these co-activators. We propose that the synergy of co-activator function between p300, CARM1 and PRMT1 is due to their different but complementary protein modification activities.
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Chan, Ho Man, and Nicholas B. La Thangue. "p300/CBP proteins: HATs for transcriptional bridges and scaffolds." Journal of Cell Science 114, no. 13 (July 1, 2001): 2363–73. http://dx.doi.org/10.1242/jcs.114.13.2363.
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p300/CBP transcriptional co-activator proteins play a central role in co-ordinating and integrating multiple signal-dependent events with the transcription apparatus, allowing the appropriate level of gene activity to occur in response to diverse physiological cues that influence, for example, proliferation, differentiation and apoptosis. p300/CBP activity can be under aberrant control in human disease, particularly in cancer, which may inactivate a p300/CBP tumour-suppressor-like activity. The transcription regulating-properties of p300 and CBP appear to be exerted through multiple mechanisms. They act as protein bridges, thereby connecting different sequence-specific transcription factors to the transcription apparatus. Providing a protein scaffold upon which to build a multicomponent transcriptional regulatory complex is likely to be an important feature of p300/CBP control. Another key property is the presence of histone acetyltransferase (HAT) activity, which endows p300/CBP with the capacity to influence chromatin activity by modulating nucleosomal histones. Other proteins, including the p53 tumour suppressor, are targets for acetylation by p300/CBP. With the current intense level of research activity, p300/CBP will continue to be in the limelight and, we can be confident, yield new and important information on fundamental processes involved in transcriptional control.
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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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MATT, Theresia, Maria A. MARTINEZ-YAMOUT, H. Jane DYSON, and Peter E. WRIGHT. "The CBP/p300 TAZ1 domain in its native state is not a binding partner of MDM2." Biochemical Journal 381, no. 3 (July 27, 2004): 685–91. http://dx.doi.org/10.1042/bj20040564.
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The transcriptional co-activator CBP [CREB (cAMP-response-element-binding protein)-binding protein] and its paralogue p300 play a key role in the regulation of both activity and stability of the tumour suppressor p53. Degradation of p53 is mediated by the ubiquitin ligase MDM2 (mouse double minute protein) and is also reported to be regulated by CBP/p300. Direct protein–protein interaction between a central domain of MDM2 and the TAZ1 (transcriptional adaptor zinc-binding domain) [C/H1 (cysteine/histidine-rich region 1)] domain of p300 and subsequent formation of a ternary complex including p53 have been reported previously. We expressed and purified the proposed binding domains of HDM2 (human homologue of MDM2) and CBP, and examined their interactions using CD spectroscopy. The binding studies were extended by using natively purified GST (glutathione S-transferase)–p300 TAZ1 and GST–p53 fusion proteins, together with in vitro translated HDM2 fragments, under similar solution conditions to those in previous studies, but omitting added EDTA, which causes unfolding and aggregation of the zinc-binding TAZ1 domain. Comparing the binding properties of the known TAZ1 interaction partners HIF-1α (hypoxia-inducible factor 1), CITED2 (CBP/p300-interacting transactivator with glutamic- and aspartic-rich tail) and STAT2 (signal transducer and activator of transcription 2) with HDM2, our data suggest that TAZ1 in its native state does not serve as a specific recognition domain of HDM2. Rather, unfolded TAZ1 and HDM2 proteins have a high tendency to aggregate, and non-specific protein complexes are formed under certain conditions.
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Li, Chia-Wei, Gia Khanh Dinh, Aihua Zhang, and J. Don Chen. "Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function." Biochemical Journal 413, no. 2 (June 26, 2008): 349–57. http://dx.doi.org/10.1042/bj20071484.
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ANCO (ankyrin repeats-containing cofactor)-1 and ANCO-2 are a family of unique transcriptional co-regulators with dual properties: they interact with both the co-activators and the co-repressors [Zhang, Yeung, Li, Tsai, Dinh, Wu, Li and Chen (2004) J. Biol. Chem. 279, 33799–33805]. Specifically, ANCO-1 is thought to recruit HDACs (histone deacetylases) to the p160 co-activator to repress transcriptional activation by nuclear receptors. In the present study, we provide new evidence to suggest further that ANCO-1 and ANCO-2 also interact with the co-activator ADA3 (alteration/deficiency in activation 3). The interaction occurs between the conserved C-terminal domain of ANCO-1 and the N-terminal transactivation domain of ADA3. Several subunits of the P/CAF {p300/CBP [CREB (cAMP-response-element-binding protein)-binding protein]-associated factor} complex, including ADA3, ADA2α/β and P/CAF, showed co-localization with ANCO-1 nuclear dots, indicating an in vivo association of ANCO-1 with the P/CAF complex. Furthermore, a transient reporter assay revealed that both ANCO-1 and ANCO-2 repress ADA3-mediated transcriptional co-activation on nuclear receptors, whereas ANCO-1 stimulated p53-mediated transactivation. These data suggest that ADA3 is a newly identified target of the ANCO proteins, which may modulate co-activator function in a transcription-factor-specific manner.
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Guidez, Fabien, Louise Howell, Mark Isalan, Marek Cebrat, Rhoda M. Alani, Sarah Ivins, Sarah Pierce, Philip A. Cole, Jonathan D. Licht, and Arthur Zelent. "Histone Acetyltransferase Activity of p300 Is Required for Transcriptional Repression by the Promyelocytic Leukemia Zinc Finger Protein." Blood 104, no. 11 (November 16, 2004): 359. http://dx.doi.org/10.1182/blood.v104.11.359.359.
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Abstract The Promyelocytic Leukemia Zinc Finger (PLZF) gene was identified in a rare case of acute promyelocytic leukemia (APL) with translocation t(11;17)(q23;q21) and resistance to therapy with all-trans-retinoic acid. Recent studies have indicated a critical role of PLZF in maintenance of spermatogonial stem cells. Prominent expression of PLZF in hematopoietic stem cells, suggest that it may also play a similar role in this compartment. The wild type PLZF protein is a DNA sequence-specific transcription repressor containing nine Krüppel-like C2-H2 zinc fingers and an N-terminal BTB/POZ repression domain. Transcriptional repression by PLZF is mediated through recruitment of the nuclear receptor co-repressor (N-CoR/SMRT)/histone deacetylase (HDAC) complexes to its target genes, such as c-MYC and HOX genes. We now show that transcriptional repression by PLZF is surprisingly also dependent on the histone acetyl transferase (HAT) activity of the p300 protein. PLZF associates with p300 in vivo and its ability to repress transcription is specifically dependent on acetylation of PLZF on lysines in its C-terminal C2-H2 zinc-finger motifs. Acetylation of PLZF enhances its ability to bind its cognate DNA binding site in vitro as determined by EMSA and in vivo as measured by chromatin immunoprecipitation. An acetylation site mutant of PLZF fails to repress transcription despite retaining its abilities to interact with co-repressor/HDAC complexes, due to inefficient DNA binding. Inhibitors of p300 abolish transcriptional repression by PLZF and mutants of PLZF that mimic acetylation were insensitive to these inhibitory effects. Acetylation of PLZF by p300 was specific since over-expression of another HAT, p/CAF or the selective inhibition of p/CAF had no effect on PLZF activity despite the ability of the proteins to associate with each other. Taken together, our results indicate that a histone deacetylase dependent transcriptional repressor can be positively regulated through acetylation and point to an unexpected role of a co-activator protein in transcriptional repression.
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Kim, Hee Eun, Eunju Bae, Deok-yoon Jeong, Min-Ji Kim, Won-Ji Jin, Sahng-Wook Park, Gil-Soo Han, George M. Carman, Eunjin Koh, and Kyung-Sup Kim. "Lipin1 regulates PPARγ transcriptional activity." Biochemical Journal 453, no. 1 (June 13, 2013): 49–60. http://dx.doi.org/10.1042/bj20121598.
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PPARγ (peroxisome-proliferator-activated receptor γ) is a master transcription factor involved in adipogenesis through regulating adipocyte-specific gene expression. Recently, lipin1 was found to act as a key factor for adipocyte maturation and maintenance by modulating the C/EBPα (CCAAT/enhancer-binding protein α) and PPARγ network; however, the precise mechanism by which lipin1 affects the transcriptional activity of PPARγ is largely unknown. The results of the present study show that lipin1 activates PPARγ by releasing co-repressors, NCoR1 (nuclear receptor co-repressor 1) and SMRT (silencing mediator of retinoid and thyroid hormone receptor), from PPARγ in the absence of the ligand rosiglitazone. We also identified a novel lipin1 TAD (transcriptional activation domain), between residues 217 and 399, which is critical for the activation of PPARγ, but not PPARα. Furthermore, this TAD is unique to lipin1 since this region does not show any homology with the other lipin isoforms, lipin2 and lipin3. The activity of the lipin1 TAD is enhanced by p300 and SRC-1 (steroid receptor co-activator 1), but not by PCAF (p300/CBP-associated factor) and PGC-1α (PPAR co-activator 1α). The physical interaction between lipin1 and PPARγ occurs at the lipin1 C-terminal region from residues 825 to 926, and the VXXLL motif at residue 885 is critical for binding with and the activation of PPARγ. The action of lipin1 as a co-activator of PPARγ enhanced adipocyte differentiation; the TAD and VXXLL motif played critical roles, but the catalytic activity of lipin1 was not directly involved. Collectively, these data suggest that lipin1 functions as a key regulator of PPARγ activity through its ability to release co-repressors and recruit co-activators via a mechanism other than PPARα activation.
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Jethanandani, Poonam, and Randall H. Kramer. "α7 Integrin Expression Is Negatively Regulated by δEF1 during Skeletal Myogenesis." Journal of Biological Chemistry 280, no. 43 (August 28, 2005): 36037–46. http://dx.doi.org/10.1074/jbc.m508698200.
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α7 integrin levels increase dramatically as myoblasts differentiate to myotubes. A negative regulatory element with putative sites for δEF1 is present in the α7 proximal promoter region. To define the role of δEF1 in regulating α7 integrin expression, we overexpressed δEF1 in C2C12 myoblasts. This resulted in a major down-regulation of α7 protein expression. Promoter assays revealed that C2C12 myoblasts transfected with δEF1 showed a decrease in activity of the 2.8-kb α7 promoter fragment, indicating regulation of α7 integrin at the transcriptional level. We have identified two E-box-like sites for δEF1 in the negative regulatory region. Mutation of these sites enhanced α7 promoter activity, indicating that these sites function in repression. MYOD, an activator of α7 integrin transcription, can compete with δEF1 for binding at these sites in gel shift assay. By using chromatin immunoprecipitation, we demonstrated a reciprocal binding of δEF1 and MYOD to this regulatory element depending on the stage of differentiation: δEF1 is preferentially bound in myoblasts to this region, whereas MYOD is bound in myotubes. The N-terminal region of δEF1 is necessary for α7 repression, and this region also binds the co-activator p300/CBP. Importantly, we found that the p300/CBP co-activator can overcome repression by δEF1, suggesting that δEF1 can titrate limiting amounts of this co-activator. These findings suggest that δEF1 has a role in suppressing integrin expression in myoblasts by displacing MYOD and competing for p300/CBP co-activator.
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SILVERMAN, Eric S., Jing DU, Amy J. WILLIAMS, Raj WADGAONKAR, Jeffrey M. DRAZEN, and Tucker COLLINS. "cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)." Biochemical Journal 336, no. 1 (November 15, 1998): 183–89. http://dx.doi.org/10.1042/bj3360183.
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Egr-1 (early-growth response factor-1) is a sequence-specific transcription factor that plays a regulatory role in the expression of many genes important for cell growth, development and the pathogenesis of disease. The transcriptional co-activators CBP (cAMP-response-element-binding-protein-binding protein) and p300 interact with sequence-specific transcription factors as well as components of the basal transcription machinery to facilitate RNA polymerase II recruitment and transcriptional initiation. Here we demonstrate a unique way in which Egr-1 physically and functionally interacts with CBP/p300 to modulate gene transcription. CBP/p300 potentiated Egr-1 mediated expression of 5-lipoxygenase (5-LO) promoter–reporter constructs, and the degree of trans-activation was proportional to the number of Egr-1 consensus binding sites present in wild-type and naturally occurring mutants of the 5-LO promoter. The N- and C-terminal domains of CBP interact with the transcriptional activation domain of Egr-1, as demonstrated by a mammalian two-hybrid assay. Direct protein–protein interactions between CBP/p300 and Egr-1 were demonstrated by glutathione S-transferase fusion-protein binding and co-immunoprecipitation/Western-blot studies. These data suggest that CBP and p300 act as transcriptional co-activators for Egr-1-mediated gene expression and that variations between individuals in such co-activation could serve as a genetic basis for variability in gene expression.
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Hyndman, Brandy D., Richard Bayly, and David P. LeBrun. "Acetylation of a Conserved Lysine Residue within Activation Domain One of E2A Transcription Factors Plays a Role in Transcriptional Regulation." Blood 108, no. 11 (November 1, 2006): 2218. http://dx.doi.org/10.1182/blood.v108.11.2218.2218.
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Abstract The E2A locus encodes transcription factors, called E12 and E47, involved in lineage-specific cellular differentiation. The locus is also involved in chromosomal translocations associated with acute lymphoblastic leukemia, the most common of which results in expression of the oncoprotein E2A-PBX1. We showed recently that direct interaction between E2A and the histone acetyl-transferase (AT) and transcriptional co-activator proteins CBP/p300 is required in leukemogenesis by E2A-PBX1. E2A proteins have also been shown to interact with another AT/co-activator, p/CAF. Interaction with these AT proteins results in acetylation of E2A proteins themselves. Here we map the acetylated lysine residues within the oncogenic portion of E2A proteins and begin to elucidate some functional correlates of E2A acetylation. Our results indicate that the isolated AT domain of p/CAF as well as full-length p/CAF were capable of acetylating E2A. Interestingly, full-length p300 was capable of acetylating E2A while an isolated AT domain was unable to acetylate E2A, suggesting that additional domains of CBP/p300 are required to mediate E2A acetylation. We demonstrate that both p300 and p/CAF can interact directly with E2A, independent of the known interaction between p300 and p/CAF. These co-activators do, however, appear to co-operate to achieve maximal E2A acetylation. Mutagenesis-based mapping studies indicate that several lysines are substrates for acetylation. Of particular interest, a conserved lysine residue (K34) located within the N-terminal transcriptional activation domain (AD1) is acetylated in vitro by p/CAF. K34 is located within a GKXXP consensus sequence, suggested to be a recognition motif for acetylation by several AT enzymes including CBP/p300 and p/CAF. Conservative replacement of K34 with arginine (i.e., K43R) substantially impairs transcriptional activation of a luciferase reporter gene by E2A, suggesting that post-translational modification of this residue may play an important functional role. Consistent with a role for acetylation, relative to some other lysine-dependent modification, we were unable to demonstrate sumoylation or ubiquitination of the N-terminus of E2A. Therefore, we have found that acetylation by AT/co-activator proteins contributes to transcriptional regulation by the functionally critical N-terminal activation domain (AD1) of E2A proteins. The mechanisms by which this acetylation event is regulated and how it contributes to target gene induction by E2A are not clear. It seems plausible that the acetylation status of AD1 could be determined by upstream signaling events and acetylation of E2A could modulate interactions with transcriptional co-regulators, DNA or chromatin. Further studies to investigate these possibilities are underway. In particular, results using an amino acid substitution that mimics acetylation of AD1 (K34Q) will be presented.
Dissertations / Theses on the topic "Protein P300 - Transcriptional Co-activator"
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Diefenbacher, Markus Elmar. "The transcriptional co-activator function of the LIM-domain protein nTrip6." Eggenstein-Leopoldshafen Forschungszentrum Karlsruhe GmbH, 2010. http://d-nb.info/1002907535/34.
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Diefenbacher, Markus Elmar [Verfasser]. "The transcriptional co-activator function of the LIM-domain protein nTrip6 / Markus Elmar Diefenbacher." Eggenstein-Leopoldshafen : Forschungszentrum Karlsruhe GmbH, 2010. http://d-nb.info/1002907535/34.
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Yagi, Ryohei. "A WW domain-containing Yes-associated protein(YAP) is a novel transcriptional co-activator." Kyoto University, 1999. http://hdl.handle.net/2433/181228.
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Diefenbacher, Markus Elmar [Verfasser], and A. [Akademischer Betreuer] Cato. "The transcriptional co-activator function of the LIM-domain protein nTrip6 / Markus Elmar Diefenbacher. Betreuer: A. Cato." Karlsruhe : KIT-Bibliothek, 2009. http://d-nb.info/1014222877/34.
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Hughes, Lucinda Jane. "Yes-Associated Protein (YAP) and Transcriptional Co-Activator with PDZ Binding Motif (TAZ) Function in Normal Cerebellar Development and Medulloblastoma." Diss., Temple University Libraries, 2016. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/412035.
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Biomedical SciencesPh.D.
The Hippo signaling pathway was first discovered in Drosophila melanogaster and is involved in organ size control by regulating cell proliferation and apoptosis. This well conserved pathway is activated by various signal inputs, including cell-cell contact, mechanotransduction, and G-protein coupled receptors, with signals converging on the downstream effector protein Yap and its homologue Taz, which are transcriptional co-activators. When the Hippo pathway is activated, Yap/Taz are phosphorylated, leading to cytoplasmic retention and degradation, and diminishing their transcriptional activity. Yap has also been recently implicated as a potential oncogene, as it is upregulated and transcriptionally active in several tumor types. Furthermore, inhibiting Yap activity in various cancer models has been shown to revert cancer cells to a normal phenotype. Although the role of Yap has been described in several organ systems, there is a paucity of information about the function of Yap in the central nervous system. I investigated the function of Yap/Taz in the murine cerebellum to determine its significance during normal development and a potential role for Yap/Taz in medulloblastoma, a tumor that arises in the cerebellum. In Chapter 2, I describe the expression pattern of Yap from embryonic through adult stages in mice, and demonstrate the functional significance of Yap/Taz in different cell populations using conditional knockout mouse models. I show that Yap plays a significant role in cell fate determination as well as in cerebellar foliation: Yap is highly expressed in the ventricular zone and is required for the proper formation of ependymal cells, and is also strongly expressed in Bergmann glia (BG) during early developmental stages, where Yap, together with Taz, plays a significant role in cerebellar foliation. Furthermore, Yap/Taz-deficient BG exhibit migrational defects, as their cell bodies can be found mislocalized to the molecular layer (ML), rather than remaining tightly associated with Purkinje Cells (PCs) in the PC layer. BG support the health of PCs, and severely defective BG positioning eventually leads to a loss of PCs. However, although Yap is highly expressed in granule neuron progenitors (GNPs) during the rapid postnatal expansion stage, it does not appear to play a major role in proliferation of these cells as conditionally knocking-out Yap/Taz in GNPs does not alter their proliferative capacity. Our observations demonstrate that in the cerebellum, Yap has a novel function in glia that is required for the development of normal foliation and organization, but plays a minimal role in GNP proliferation. Importantly, I also show that the reduction of sphingosine-1-phosphate G-protein-coupled receptor (S1P1) signal transduction activates the upstream kinase Lats with concomitant increases of phosphorylated Yap as well as a reduction of the known Yap target connective tissue growth factor (CTGF). This study identifies a novel function of Yap/Taz in cerebellar glia that is required for the development of normal foliation and laminar organization with sphingosine-1-phosphate (S1P) signaling as a potential extracellular cue regulating Yap activity during cerebellar development. In Chapter 3, I present further support for the finding that Yap/Taz are not required for GNP proliferation in vivo by discussing the failure of Yap/Taz loss to rescue the Sonic-hedgehog (Shh) mediated medulloblastoma phenotype, in which GNPs are considered to be the tumor cell of origin. Furthermore, I provide evidence suggestive of a tumor suppressive function of Yap/Taz in the cerebellum. Together, previously unknown functions of Yap in the developing and malignant cerebellum are described, providing a foundation for future studies of Yap in the central nervous system (CNS).
Temple University--Theses
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Kirlin, Alyssa. "Elucidation of the interactions between the transcription factor E2A and the transcriptional co-activator CBP/p300." Thesis, 2013. http://hdl.handle.net/1974/8149.
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E2A is a transcription factor that plays a particularly critical role in lymphopoiesis. The chromosomal translocation 1;19, disrupts the E2A gene and results in the expression of the fusion oncoprotein E2A-PBX1, which is implicated in acute lymphoblastic leukemia. Both E2A and E2A-PBX1 contain two activation domains, AD1 and AD2, which comprise conserved ΦxxΦΦ motifs where Φ denotes a hydrophobic amino acid. These domains function to recruit transcriptional co-activators and repressors, including the histone acetyl transferase CREB binding protein (CBP) and its paralog p300. The PCET motif within E2A AD1 interacts with the KIX domain of CBP/p300, the disruption of which abrogates the transcriptional activation by E2A and the transformative properties of E2A-PBX1. The generation of a peptide-based inhibitor targeting the PCET:KIX interaction would serve useful in further assessing the role of E2A and E2A-PBX1 in lymphopoiesis and leukemogenesis. An interaction between E2A AD2 and the KIX domain has also been recently identified, and the TAZ domains of CBP/p300 have been shown to interact with several transcription factors that contain ΦxxΦΦ motifs. Thus the design of an inhibitor of the E2A:CBP/p300 interaction requires the full complement of interactions between E2A and the various domains of CBP/p300 to be elucidated. Here, we have used nuclear magnetic resonance (NMR) spectroscopy to determine that AD2 interacts with KIX at the same site as PCET, which indicates that the E2A:KIX interaction can be disrupted by targeting a single binding site. Using an iterative synthetic peptide microarray approach, a peptide with the sequence DKELQDLLDFSLQY was derived from PCET to interact with KIX with higher affinity than the wild type sequence. This peptide now serves as a lead molecule for further development as an inhibitor of the E2A:CBP/p300 interaction. Fluorescence anisotropy, peptide microarray technology, and isothermal titration calorimetry were employed to characterize interactions between both TAZ domains of CBP/p300 and the PCET motif and AD2 of E2A. Alanine substitution of residues within PCET demonstrated that the ΦxxΦΦ motif is a key mediator of these interactions, analogous to the PCET:KIX interaction. These findings now inform future work to establish possible physiological roles for the E2A:TAZ1 and E2A:TAZ2 interactions.Thesis (Master, Biochemistry) -- Queen's University, 2013-08-06 13:52:28.248
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Irrcher, Isabella. "Regulation of the transcriptional co-activator PGC-1alpha in skeletal muscle cells /." 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR32052.
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Thesis (Ph.D.)--York University, 2007. Graduate Programme in Biology.Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR32052
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Hsu, Wei-Shan. "Drosophila decapping protein 1,dDcp1, is a putative TGF- signaling transcriptional co-activator." 2004. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2707200411452000.
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Hsu, Wei-Shan, and 徐唯珊. "Drosophila decapping protein 1,dDcp1, is a putative TGF-β signaling transcriptional co-activator." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/45709144974737696421.
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碩士國立臺灣大學
分子與細胞生物學研究所
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CG11183 is the Drosophila homology of SMIF and was named as dSMIF first. SMIF is identified as a transcriptional co-activator in transforming growth factor-β (TGF-β) signaling pathway and it also has decapping activity. Therefore, SMIF is also named as hDcp1a. However, there is no genetic evidence to link CG11183 with Drosophila TGF-β signaling. Moreover, CG11183 was later found to have the intrinsic decapping activity. Therefore, we named CG11183 as Drosophila decapping protein 1(dDcp1). In order to clarify the relationship between dDcp1 and TGF-β signaling pathway, we approached this aim in three aspects. First, to investigate the possible interaction between dDcp1 and the members in Drosophila TGF-β signaling pathway by yeast two/three-hybrid assay. Second, to create a dDcp1 null allele by imprecise excision screen. Third, to analyze the dDcp1 null phenotype and try to get the direct evidences to connect dDcp1 with TGF-β signaling. From the one/two/three-hybrid assay, we proved that dDcp1 can interact not only with the Drosophila Co-Smad, Medea, but also with the two Drosophila R-Smads, Mad and dSmad2. It was also certified that dDcp1, R-Smad and Co-Smad form a trimer. Further, dDcp1 is considered to have the ability to form oligomer and has the transactivation activity at the C-terminal. These results imply that dDcp1 is a putative transcriptional co-activator in TGF-β signaling. After two imprecise excision screens, dDcp1442pop was verified as a null allele. The imaginal discs and potic lobes can not development in dDcp1442pop larvae. Moreover, dDcp1442pop larvae displayed lower EcR-B1 expression in the central brain. These indicate that dDcp1 is a putative tissue-specific transcriptional co-activator in TGF-β signaling.
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加畑, 馨. "Regulation of transforming growth factor-β and bone morphogenetic protein signaling by transcriptional co-activator GCN5." Doctoral thesis, 2004. http://hdl.handle.net/2115/32665.
Full textConference papers on the topic "Protein P300 - Transcriptional Co-activator"
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Romano, Simona, Giovanna Nappo, Elena Cesaro, Antonio Candela, and Maria Fiammetta Romano. "Abstract 755: FK506 binding protein 51 (FKBP51) binds to p300 and acts as transcriptional co-regulator of ABCG2 gene expression in melanoma." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-755.
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