Relevant bibliographies by topics / OTUB1

Academic literature on the topic 'OTUB1'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "OTUB1"

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Sivakumar, Dakshinamurthy, Vikash Kumar, Michael Naumann, and Matthias Stein. "Activation and selectivity of OTUB-1 and OTUB-2 deubiquitinylases." Journal of Biological Chemistry 295, no. 20 (April 7, 2020): 6972–82. http://dx.doi.org/10.1074/jbc.ra120.013073.

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The ovarian tumor domain (OTU) deubiquitinylating cysteine proteases OTUB1 and OTUB2 (OTU ubiquitin aldehyde binding 1 and 2) are representative members of the OTU subfamily of deubiquitinylases. Deubiquitinylation critically regulates a multitude of important cellular processes, such as apoptosis, cell signaling, and growth. Moreover, elevated OTUB expression has been observed in various cancers, including glioma, endometrial cancer, ovarian cancer, and breast cancer. Here, using molecular dynamics simulation approaches, we found that both OTUB1 and OTUB2 display a catalytic triad characteristic of proteases but differ in their configuration and protonation states. The OTUB1 protein had a prearranged catalytic site, with strong electrostatic interactions between the active-site residues His265 and Asp267. In OTUB2, however, the arrangement of the catalytic triad was different. In the absence of ubiquitin, the neutral states of the catalytic-site residues in OTUB2 were more stable, resulting in larger distances between these residues. Only upon ubiquitin binding did the catalytic triad in OTUB2 rearrange and bring the active site into a catalytically feasible state. An analysis of water access channels revealed only a few diffusion trajectories for the catalytically active form of OTUB1, whereas in OTUB2 the catalytic site was solvent-accessible, and a larger number of water molecules reached and left the binding pocket. Interestingly, in OTUB2, the catalytic residues His224 and Asn226 formed a stable hydrogen bond. We propose that the observed differences in activation kinetics, protonation states, water channels, and active-site accessibility between OTUB1 and OTUB2 may be relevant for the selective design of OTU inhibitors.
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Edelmann, Mariola J., Alexander Iphöfer, Masato Akutsu, Mikael Altun, Katalin di Gleria, Holger B. Kramer, Edda Fiebiger, Sirano Dhe-Paganon, and Benedikt M. Kessler. "Structural basis and specificity of human otubain 1-mediated deubiquitination." Biochemical Journal 418, no. 2 (February 11, 2009): 379–90. http://dx.doi.org/10.1042/bj20081318.

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OTUB (otubain) 1 is a human deubiquitinating enzyme that is implicated in mediating lymphocyte antigen responsiveness, but whose molecular function is generally not well defined. A structural analysis of OTUB1 shows differences in accessibility to the active site and in surface properties of the substrate-binding regions when compared with its close homologue, OTUB2, suggesting variations in regulatory mechanisms and substrate specificity. Biochemical analysis reveals that OTUB1 has a preference for cleaving Lys48-linked polyubiquitin chains over Lys63-linked polyubiquitin chains, and it is capable of cleaving NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8), but not SUMO (small ubiquitin-related modifier) 1/2/3 and ISG15 (interferon-stimulated gene 15) conjugates. A functional comparison of OTUB1 and OTUB2 indicated a differential reactivity towards ubiquitin-based active-site probes carrying a vinyl methyl ester, a 2-chloroethyl or a 2-bromoethyl group at the C-terminus. Mutational analysis suggested that a narrow P1′ site, as observed in OTUB1, correlates with its ability to preferentially cleave Lys48-linked ubiquitin chains. Analysis of cellular interaction partners of OTUB1 by co-immunoprecipitation and MS/MS (tandem mass spectrometry) experiments demonstrated that FUS [fusion involved in t(12;6) in malignant liposarcoma; also known as TLS (translocation in liposarcoma) or CHOP (CCAAT/enhancer-binding protein homologous protein)] and RACK1 [receptor for activated kinase 1; also known as GNB2L1 (guanine-nucleotide-binding protein β polypeptide 2-like 1)] are part of OTUB1-containing complexes, pointing towards a molecular function of this deubiquitinating enzyme in RNA processing and cell adhesion/morphology.
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Thanh Huyen, Nguyen, Nguyen Hoang Giang, and Nguyen Thi Xuan. "Expression of deubiquitinase genes and inflammatory response in myeloid leukemia." Vietnam Journal of Biotechnology 20, no. 3 (September 30, 2022): 401–8. http://dx.doi.org/10.15625/1811-4989/16428.

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Myeloid leukemia (ML) is a cancer of the blood that begins when cells of the myeloid lineage uncontrollably change and grow. Acute myeloid leukemia (AML) is a disorder of rapid, uncontrolled growth of immature myeloid cells in the blood and bone marrow. Chronic myeloid leukemia (CML) is characterized by the aberrant proliferation of myeloid cells and driven by the translocation of regions of the BCR and ABL genes to form the Philadelphia (Ph) chromosome. The deubiquitinase enzymes (DUBs) including A20, OTUB1, OTUB2, and Cezanne play important roles in inhibiting NF-κB activation in response to various stimuli. Cytokines including tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β are released from immune cell activation triggered by antigenic stimulation. To this end, blood samples of 20 AML and 62 CML patients and the control group consisting of 37 healthy individuals were used to examine the mRNA expression of A20, OTUB1, OTUB2 and Cezanne genes by using quantitative RT-PCR and determine IL-6, TNF-α and IL-1β concentrations by using ELISA. As a result, the mRNA level of OTUB1 was significantly decreased in both AML and CML patients compared to that in healthy individuals, however, no difference in the transcriptional expression of OTUB2 among AML and CML patients and control group was detected. Unlike the levels of OTUB1 and OTUB2, the expressions of A20 and Cezanne in CML, but not in AML patients were significantly lower than healthy individuals. For serum cytokine analysis of the study groups, in AML and CML samples, IL-6 and TNF-α concentrations significantly increased in comparison with the control group, however, IL-1β level was similar among CML, AML patients and healthy individuals. In conclusion, this study revealed the different DUB involvement in the pathogenesis of ML, suggesting further investigations on gene polymorphisms and their functions linked to biological properties of leukemia cells.
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Pasupala, Nagesh, Marie E. Morrow, Lauren T. Que, Barbara A. Malynn, Averil Ma, and Cynthia Wolberger. "OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination." Journal of Biological Chemistry 293, no. 47 (October 3, 2018): 18285–95. http://dx.doi.org/10.1074/jbc.ra118.004677.

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OTUB1 is a deubiquitinating enzyme that cleaves Lys-48–linked polyubiquitin chains and also regulates ubiquitin signaling through a unique, noncatalytic mechanism. OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and inhibits their activity by trapping the E2∼ubiquitin thioester and preventing ubiquitin transfer. The same set of E2s stimulate the deubiquitinating activity of OTUB1 when the E2 is not charged with ubiquitin. Previous studies have shown that, in cells, OTUB1 binds to E2-conjugating enzymes of the UBE2D (UBCH5) and UBE2E families, as well as to UBE2N (UBC13). Cellular roles have been identified for the interaction of OTUB1 with UBE2N and members of the UBE2D family, but not for interactions with UBE2E E2 enzymes. We report here a novel role for OTUB1–E2 interactions in modulating E2 protein ubiquitination. We observe that Otub1−/− knockout mice exhibit late-stage embryonic lethality. We find that OTUB1 depletion dramatically destabilizes the E2-conjugating enzyme UBE2E1 (UBCH6) in both mouse and human OTUB1 knockout cell lines. Of note, this effect is independent of the catalytic activity of OTUB1, but depends on its ability to bind to UBE2E1. We show that OTUB1 suppresses UBE2E1 autoubiquitination in vitro and in cells, thereby preventing UBE2E1 from being targeted to the proteasome for degradation. Taken together, we provide evidence that OTUB1 rescues UBE2E1 from degradation in vivo.
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Baek, Suk-Hwan, and Han Zhong Pei. "Ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 inhibits IL-6 production by regulating Nur77 stability." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 52.6. http://dx.doi.org/10.4049/jimmunol.202.supp.52.6.

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Abstract Nur77 (NR4A1) plays an important role in various cellular responses such as apoptosis and inflammation. Nur77 is rapidly degraded in cells and its protein level is critically controlled. Although few ubiquitin E3 ligases regulating the Nur77 protein have been defined, the deubiquitinase (DUB) responsible for Nur77 stability has not been reported to date. We identified ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) as a DUB that stabilizes Nur77 by preventing its proteasomal degradation. We found that OTUB1 interacted with Nur77 to deubiquitinate it, thereby stabilizing Nur77 in an Asp88-dependent manner. This suggests that OTUB1 targets Nur77 for deubiquitination via a non-canonical mechanism. Moreover, we confirmed that OTUB1 reverses ubiquitination of the K48-linked chains in Nur77. Functionally, OTUB1 inhibited TNFα-induced IL-6 production by promoting Nur77 protein stability. OTUB1 modulated the stability of Nur77 as a counterpart of tripartite motif 13 (Trim13). That is, OTUB1 reduced the ubiquitination and degradation of Nur77 potentiated by Trim13. In addition, this DUB also inhibited IL-6 production, which was further amplified by Trim13 in TNFα-induced IL-6 production. These findings suggest that OTUB1 is an important regulator of Nur77 stability and plays a role in controlling the inflammatory response.
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Ruiz-Serrano, Amalia, Christina Boyle, Josep Monné Rodríguez, Julia Günter, Agnieszka Jucht, Svende Pfundstein, Andreas Bapst, Thomas Lutz, Roland Wenger, and Carsten Scholz. "The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism." International Journal of Molecular Sciences 23, no. 3 (January 28, 2022): 1536. http://dx.doi.org/10.3390/ijms23031536.

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Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.
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Koschel, Josephin, Gopala Nishanth, Sissy Just, Kunjan Harit, Andrea Kröger, Martina Deckert, Michael Naumann, and Dirk Schlüter. "OTUB1 prevents lethal hepatocyte necroptosis through stabilization of c-IAP1 during murine liver inflammation." Cell Death & Differentiation 28, no. 7 (March 12, 2021): 2257–75. http://dx.doi.org/10.1038/s41418-021-00752-9.

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AbstractIn bacterial and sterile inflammation of the liver, hepatocyte apoptosis is, in contrast to necroptosis, a common feature. The molecular mechanisms preventing hepatocyte necroptosis and the potential consequences of hepatocyte necroptosis are largely unknown. Apoptosis and necroptosis are critically regulated by the ubiquitination of signaling molecules but especially the regulatory function of deubiquitinating enzymes (DUBs) is imperfectly defined. Here, we addressed the role of the DUB OTU domain aldehyde binding-1 (OTUB1) in hepatocyte cell death upon both infection with the hepatocyte-infecting bacterium Listeria monocytogenes (Lm) and D-Galactosamine (DGal)/Tumor necrosis factor (TNF)-induced sterile inflammation. Combined in vivo and in vitro experiments comprising mice lacking OTUB1 specifically in liver parenchymal cells (OTUB1LPC-KO) and human OTUB1-deficient HepG2 cells revealed that OTUB1 prevented hepatocyte necroptosis but not apoptosis upon infection with Lm and DGal/TNF challenge. Lm-induced necroptosis in OTUB1LPC-KO mice resulted in increased alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release and rapid lethality. Treatment with the receptor-interacting serine/threonine-protein kinase (RIPK) 1 inhibitor necrostatin-1s and deletion of the pseudokinase mixed lineage kinase domain-like protein (MLKL) prevented liver damage and death of infected OTUB1LPC-KO mice. Mechanistically, OTUB1 reduced K48-linked polyubiquitination of the cellular inhibitor of apoptosis 1 (c-IAP1), thereby diminishing its degradation. In the absence of OTUB1, c-IAP1 degradation resulted in reduced K63-linked polyubiquitination and increased phosphorylation of RIPK1, RIPK1/RIPK3 necrosome formation, MLKL-phosphorylation and hepatocyte death. Additionally, OTUB1-deficiency induced RIPK1-dependent extracellular-signal-regulated kinase (ERK) activation and TNF production in Lm-infected hepatocytes. Collectively, these findings identify OTUB1 as a novel regulator of hepatocyte-intrinsic necroptosis and a critical factor for survival of bacterial hepatitis and TNF challenge.
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Kumari, Raniki, Roshan Kumar, Sanjay Kumar, Abhishek Kumar Singh, Pranita Hanpude, Deepak Jangir, and Tushar Kanti Maiti. "Amyloid aggregates of the deubiquitinase OTUB1 are neurotoxic, suggesting that they contribute to the development of Parkinson's disease." Journal of Biological Chemistry 295, no. 11 (January 31, 2020): 3466–84. http://dx.doi.org/10.1074/jbc.ra119.009546.

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Parkinson's disease (PD) is a multifactorial malady and the second most common neurodegenerative disorder, characterized by loss of dopaminergic neurons in the midbrain. A hallmark of PD pathology is the formation of intracellular protein inclusions, termed Lewy bodies (LBs). Recent MS studies have shown that OTU deubiquitinase ubiquitin aldehyde-binding 1 (OTUB1), a deubiquitinating enzyme of the OTU family, is enriched together with α-synuclein in LBs from individuals with PD and is also present in amyloid plaques associated with Alzheimer's disease. In the present study, using mammalian cell cultures and a PD mouse model, along with CD spectroscopy, atomic force microscopy, immunofluorescence-based imaging, and various biochemical assays, we demonstrate that after heat-induced protein aggregation, OTUB1 reacts strongly with both anti-A11 and anti-osteocalcin antibodies, detecting oligomeric, prefibrillar structures or fibrillar species of amyloidogenic proteins, respectively. Further, recombinant OTUB1 exhibited high thioflavin-T and Congo red binding and increased β-sheet formation upon heat induction. The oligomeric OTUB1 aggregates were highly cytotoxic, characteristic of many amyloid proteins. OTUB1 formed inclusions in neuronal cells and co-localized with thioflavin S and with α-synuclein during rotenone-induced stress. It also co-localized with the disease-associated variant pS129-α-synuclein in rotenone-exposed mouse brains. Interestingly, OTUB1 aggregates were also associated with severe cytoskeleton damage, rapid internalization inside the neuronal cells, and mitochondrial damage, all of which contribute to neurotoxicity. In conclusion, the results of our study indicate that OTUB1 may contribute to LB pathology through its amyloidogenic properties.
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Kim, Soomi, Kibeom Park, Jung-Min Oh, and Hongtae Kim. "RNF126 is a positive regulator of TRAF3 ubiquitination." Bioscience, Biotechnology, and Biochemistry 85, no. 12 (October 13, 2021): 2420–28. http://dx.doi.org/10.1093/bbb/zbab177.

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ABSTRACT Ubiquitination and deubiquitination of signaling molecules are critical regulatory mechanisms in various biological contexts such as inflammatory signaling and the DNA damage response. Thus, finely tuned regulation of protein ubiquitination is essential for maintaining cellular homeostasis. Here, we showed that the RING finger protein RNF126 interacts with TRAF3 and promotes its K63-linked polyubiquitination, which is a crucial step in the TRAF3-dependent antiviral response. We found that RNF126 also interacts with OTUB1, a deubiquitinating enzyme that negatively regulates K63-linked ubiquitination of TRAF3. RNF126 promotes ubiquitination of OTUB1, leading to reduced deubiquitinating activity toward TRAF3. Moreover, RNF126 promotes ubiquitination of OTUB1 on cysteine 91, which is reportedly required for its catalytic activity. Taken together, our results suggest that RNF126 positively regulates the antiviral response by directly promoting K63-linked polyubiquitination of TRAF3 and by reducing OTUB1 activity.
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Saldana, Matthew, Kacey VanderVorst, Anastasia L. Berg, Hyun Lee, and Kermit L. Carraway. "Otubain 1: a non-canonical deubiquitinase with an emerging role in cancer." Endocrine-Related Cancer 26, no. 1 (January 2019): R1—R14. http://dx.doi.org/10.1530/erc-18-0264.

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The ubiquitin system regulates diverse biological processes, many involved in cancer pathogenesis, by altering the ubiquitination state of protein substrates. This is accomplished by ubiquitin ligases and deubiquitinases (DUBs), which respectively add or remove ubiquitin from substrates to alter their stability, activity, localization and interactions. While lack of catalytic activity makes therapeutic targeting of ubiquitin ligases difficult, DUB inhibitors represent an active area of research and the identification of cancer-associated DUBs may lead to the development of novel therapeutics. A growing body of literature demonstrates that the DUB Otubain 1 (OTUB1) regulates many cancer-associated signaling pathways including MAPK, ERa, epithelial-mesenchymal transition (EMT), RHOa, mTORC1, FOXM1 and P53 to promote tumor cell survival, proliferation, invasiveness and therapeutic resistance. In addition, clinical studies have associated elevated OTUB1 expression with high grade, invasiveness and metastasis in several tumor types including lung, breast, ovarian, glioma, colon and gastric. Interestingly, in addition to catalytic DUB activity, OTUB1 displays a catalytic-independent, non-canonical activity where it inhibits the transfer of ubiquitin onto protein substrates by sequestration of E2 ubiquitin-conjugating enzymes. The aim of this review is to describe the canonical and non-canonical activities of OTUB1, summarize roles for OTUB1 in cancer-associated pathways and discuss its potential therapeutic targeting.
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Dissertations / Theses on the topic "OTUB1"

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Zulkifle, Nurulisa. "Analysis of binary interactions between OTUB1 and E2 ubiquitin-conjugating enzymes." Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/8033/.

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Post-translational modification of proteins via ubiquitination is mediated by three enzyme families; E1 activating enzymes, E2 conjugating enzymes and E3 ligases, all of which work in a hierarchical manner to facilitate different forms of protein ubiquitin ranging from mono-ubiquitination to the formation of different forms of ubiquitin chains (Ciechanover et al., 2000). Deubiquitinating enzymes (DUBs) act to remove ubiquitin from modified substrates. Apart from the classic interactions within the E1-E2-E3 enzymatic cascade, an unusual non-hierarchical interaction has been observed between some E2 enzymes and a DUB called OTUB1 (Markson et al., 2009). This observation raises interesting questions concerning the molecular mechanisms and specificity of this unusual E2:DUB partnership. In this study, systematic yeast two-hybrid (Y2H) screens were performed between all human E2 and DUB proteins to analyse the extent of E2:DUB interactions. Putative partnerships between OTUB1 and UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3 and UBE2N were identified. These data correlate well with data from other independent studies, including HTP Y2H screens (Markson et al., 2009) and mass spectrometry (Sowa et al., 2009). An N-terminal truncated form of OTUB1 (ΔNOTUB1) was generated by removing a predicted 39aa N-terminal disordered region (Edelmann et al., 2009). Using this construct in combination with wild type (WT) OTUB1, complementary biophysical studies were performed to investigate the formation of complexes with UBE2D2 and UBE2E1 as these represented the strongest interactions detected in preliminary Y2H studies. Gel filtration chromatography showed convincing complex formation for both ΔNOTUB1:UBE2D2 and ΔNOTUB1:UBE2E1 in 1:1 stoichiometry. The thermodynamic profile of each complex was measured by ITC suggested a stronger affinity between ΔNOTUB1:UBE2D2 (Kd 3.89 µM) than observed for the ΔNOTUB1:UBE2E1 complex (Kd 16.55 µM). The n values for both complexes are 1.16±0.06 sites and 0.92±0.03 sites respectively, confirming that both complexes adopt a 1:1 stoichiometry. Observing the UBE2D2 (1H15N)-HSQC NMR spectral changes that occurred upon addition of unlabelled ΔNOTUB1 allowed the identification of potential residues of contact between the two proteins. From this study, we were able to predict that the 1st α-helix, the L1 loop of the 3rd and 4th β-sheet, the L2 loop connecting the 4th β-strand and the H2 α-helix within UBE2D2 were likely to be the binding surfaces for OTUB1. Point mutants corresponding to predicted contact residues in UBE2D2 were generated and tested in Y2H studies to determine their role in facilitating the formation of both E2:OTUB1 and E2:E3-RING complexes. This data suggests that in some, but not all cases, OTUB1 and E3-RINGs bind competitively to the same interface on E2 proteins. Preliminary immunofluorescence studies show that partner proteins predominantly co-localise in the cytoplasm, except UBE2E1 which is predominantly nuclear. Data from this study allowed us to propose a model of how OTUB1:UBE2D2 complex may forms and functions. Significantly, many of these predictions have now been verified by independent structural studies and subsequent live cell microscopy studies in our lab.
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Koschel, Josephin [Verfasser]. "Hepatocyte-specific role of the deubiquitinating enzyme OTUB1 during inflammatory liver diseases / Josephin Koschel." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2020. http://d-nb.info/122807173X/34.

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Mulas, Floriana [Verfasser], and Dirk [Gutachter] Schlüter. "Dendritic cell-specific function of OTUB1 in inflammation and infection / Floriana Mulas ; Gutachter: Dirk Schlüter." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2020. http://d-nb.info/122267064X/34.

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Mulas, Floriana Verfasser], and Dirk [Gutachter] [Schlüter. "Dendritic cell-specific function of OTUB1 in inflammation and infection / Floriana Mulas ; Gutachter: Dirk Schlüter." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2020. http://d-nb.info/122267064X/34.

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Gil, Mir Maria Eugenia. "Expanding the MDM2 interactome." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25781.

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p53 is a key component of the protein network that regulates cell cycle progression and prevents cancer. Under non-stressed conditions, its activity is controlled by an autoregulatory feedback loop with MDM2 that maintains low levels of the p53 protein. However, in response to stress signals, p53 is triggered to become active. MDM2 has been reported to regulate p53 by a combination of mechanisms: ubiquitination using its E3-ligase capability, chaperone activity in an ATP-dependent manner and directly transrepressing p53. Because of MDM2's central role in the control of p53, it has been the target of intense drug development efforts. A family of small molecules, the Nutlins, can bind to an MDM2 pocket modulating the p53: MDM2 complex. This leads to p53 activation and growth inhibitory effects. The aim of our study was to analyse the interactome of endogenous MDM2 and to determine whether anti-cancer drugs, such as Nutlin-3, could stabilise or disrupt sets of MDM2 interactions in order to better understand the p53- dependent and independent functions of MDM2 as a signalling hub, as well as the p53-independent activity of Nutlin-3. Results show a remarkable difference in the sets of proteins found in MDM2 complexes in control and Nutlin-3 treated cells. Two proteins, TRIM25 and OTUB2, were selected from the output list for validation based on their known functions in the ubiquitin signalling network. Binding has been studied in detail and confirmed using both in cell and in vitro techniques. The data highlight potentially novel functions for MDM2 and provides insight into the on-target p53-independent activities of Nutlin-3. Additionally, and with the aim of blocking p53 ubiquitination by MDM2, I have developed probes that are able to inhibit the ubiquitylation of p53 in vitro.
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Fabrizio, Jacqueline Alba. "Characterising Novel Substrates of the Asparaginyl Hydroxylase FIH." Thesis, 2017. https://hdl.handle.net/2440/132758.

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Factor Inhibiting the Hypoxia Inducible Factor (FIH) is an oxygen-dependent asparaginyl hydroxylase that plays a role in the cellular response to changes in oxygen concentrations. It was first found to catalyse the post translational hydroxylation of a family of transcription factors known as Hypoxia Inducible Factors (HIFs), and thus acts as a cellular sensor of hypoxia. Subsequently, other protein substrates were discovered containing ankyrin (ANK) repeat domains, although their activities were not affected by hydroxylation. FIH null mice display a metabolic phenotype which is not obviously linked to HIF regulation, supporting the existence of other important substrates of FIH. Hence the search for novel substrates of FIH was pursued, with particular interest in target proteins that upon modification by FIH would have a functional cellular outcome. Methods such as yeast two hybrid and pull down assays were previously employed to discover new substrates of FIH, but this limited searches to proteins with a relatively strong affinity for FIH. In research by a collaborator, a non-biased bioinformatic search was used to identify novel potential FIH substrates. Interestingly, the search identified a family of 5 ANK proteins present in the Orf virus (ORFV) as likely substrates of FIH. Preliminary experiments in our laboratory showed that they could interact with human FIH (hFIH), and some showed activity in CO₂ capture assays, consistent with hydroxylation. The first aim of this thesis was to determine whether the 5 ORFV ANK proteins, 008, 123, 126, 128 and 129 were substrates of FIH. Given that ORFV is an ovine virus, ovine FIH (oFIH) was cloned and purified, with recombinant protein displaying similar activity to recombinant hFIH. The ORFV ANK domains were cloned, expressed in bacteria and purified for analysis with recombinant oFIH. The hydroxylation state of these proteins was first analysed indirectly using in vitro hydroxylation assay and 008, 126 and 129 displayed high activity, consistent with being effectively hydroxylated by FIH, whereas 123 and 128 displayed low activity. Mass spectrometry (MS) of the recombinant proteins confirmed FIH-mediated hydroxylation of N40 in 008, N285 in 126, and N44 in 129, with poor ionisation preventing definitive conclusions regarding hydroxylation of 123 and 128. The ANK proteins of another closely related poxvirus, vaccinia virus (VACV), were also predicted to be substrates of FIH, but analysis of recombinant VACV ANK proteins showed no evidence of hydroxylation. These data indicate that these hydroxylation events are not conserved across the poxvirus family. The second aim was to characterise the functional role for this interaction between ORFV ANK proteins and FIH. Given the poorly characterised roles of the ORFV ANK proteins, and the relatively stable interaction between these proteins and FIH, these studies focused on the hypothesis that the ORFV ANK proteins could sequester FIH and subsequently upregulate HIF activity upon viral infection. Cell-based reporter gene assays confirmed that expression of the ORFV ANKs could sequester FIH and upregulate the HIFα transactivation domain, leading to increased HIF activity. Further supporting this hypothesis, ORFV infected cells that overexpressed or were deficient in FIH showed the induction of well characterised HIF target genes in a FIH-dependent manner. These data identified a novel mechanism of viral induced modulation of HIF activity, via the sequestration of FIH. The final aim of this thesis was to analyse OTUB1, a non-ANK and non-HIF protein discovered by our collaborators as a putative novel substrate of FIH. The hydroxylation of OTUB1 on N22 by FIH in vitro was confirmed using synthetic OTUB1 peptides in CO₂ capture assays.
Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 2018
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Otube, Nelly Were [Verfasser]. "Job motivation of teachers educating learners with special needs in four provinces in Kenya = Berufsmotivation von Lehrern von Schülern mit sonderpädagogischen Förderbedarf in vier Provinzen Kenias / Nelly Were Otube." 2004. http://d-nb.info/972269665/34.

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Book chapters on the topic "OTUB1"

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Weber, Elisabeth, Kenji Schorpp, and Kamyar Hadian. "Studying OTUD6B-OTUB1 Protein–Protein Interaction by Low-Throughput GFP-Trap Assays and High-Throughput AlphaScreen Assays." In Methods in Molecular Biology, 381–94. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1186-9_23.

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Drag, Marcin. "OTU1 Peptidase." In Handbook of Proteolytic Enzymes, 2121–23. Elsevier, 2013. http://dx.doi.org/10.1016/b978-0-12-382219-2.00477-4.

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Conference papers on the topic "OTUB1"

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Li, Yuhunag, Xiao-Xin Sun, Johannes Elferich, Ujwal Shinde, Larry David, and Mushui Dai. "Abstract LB-308: Monoubiquitination is critical for Otub1 to suppress UbcH5 and stabilize p53." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-lb-308.

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Laurent, BIGOT, JURDYC Anne-Marie, JACQUIER Bernard, GASCA Laurent, MOREAU Christine, BANIEL Pascal, and BAYART Dominique. "Homogeneous and inhomogeneous broadening measurements of EDFA C and L bands." In Optical Amplifiers and Their Applications. Washington, D.C.: OSA, 2001. http://dx.doi.org/10.1364/oaa.2001.otub1.

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Sotobayashi, Hideyuki. "OCDM techniques for improved spectral densities." In Optical Amplifiers and Their Applications. Washington, D.C.: OSA, 2002. http://dx.doi.org/10.1364/oaa.2002.otub1.

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Nolting, Hans-Peter. "All-optical signal processing using ultra-long SOAs." In Optical Amplifiers and Their Applications. Washington, D.C.: OSA, 2004. http://dx.doi.org/10.1364/oaa.2004.otub1.

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Pálsdóttir, Bera, Peter B. Gaarde, and Torben Veng. "Requirements for erbium doped fibers and dispersion compensating fibers in high performance amplifiers." In Optical Amplifiers and Their Applications. Washington, D.C.: OSA, 2006. http://dx.doi.org/10.1364/oaa.2006.otub1.

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Symington, K. J., A. J. Waddie, T. Yasue, M. R. Taghizadeh, and J. F. Snowdon. "High Performance Optoelectronic Neural Network Scheduler." In Optics in Computing. Washington, D.C.: OSA, 2001. http://dx.doi.org/10.1364/oc.2001.otub1.

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Hase, Muneaki, Kotaro Makino, and Junji Tominaga. "Ultrafast Coherent Switching of Phase-Change in Rewritable Optical Media." In Joint International Symposium on Optical Memory and Optical Data Storage. Washington, D.C.: OSA, 2011. http://dx.doi.org/10.1364/isom_ods.2011.otub1.

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Chowdhury, Arshad, Hung-Chang Chien, Jianjun Yu, and Gee-Kung Chang. "A Novel 50-GHz Spaced DWDM 60-GHz Millimeter-Wave Radio-over-Fiber Systems using Optical Interleaver." In Optical Fiber Communication Conference. Washington, D.C.: OSA, 2009. http://dx.doi.org/10.1364/ofc.2009.otub1.

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Reid, Jonathan P., and Jon B. Wills. "Optical Control of Aerosols." In Optical Trapping Applications. Washington, D.C.: OSA, 2009. http://dx.doi.org/10.1364/ota.2009.otub1.

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Vo, T. D., M. D. Pelusi, J. Schröder, F. Luan, S. J. Madden, D. Y. Choi, D. A. P. Bulla, B. Luther-Davies, and B. J. Eggleton. "All-optical multi-impairment performance monitoring of 640 Gb/s optical signals using a chalcogenide photonic chip." In Optical Fiber Communication Conference. Washington, D.C.: OSA, 2010. http://dx.doi.org/10.1364/ofc.2010.otub1.

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