The OTUD5–UBR5 complex regulates FACT-mediated transcription at damaged chromatin

Vivo, Angelo de; Sanchez, Anthony; Yegres, Jose; Kim, Jeonghyeon; Emly, Sylvia M.; Kee, Younghoon

doi:10.1093/nar/gky1219

Cited by 56 publications

(49 citation statements)

References 53 publications

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“…First, OTUD5 interacts with UBR5 and represses RNA Pol II-mediated elongation and RNA synthesis. In addition, OTUD5 interacts with the FACT component SPT16 and antagonizes histone H2A deposition at DSBs [67].…”

Section: Dubs and The Ddrmentioning

confidence: 99%

Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy

Lai

Chen

Tse

2020

IJMS

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Deubiquitinases (DUBs) are involved in various cellular functions. They deconjugate ubiquitin (UBQ) from ubiquitylated substrates to regulate their activity and stability. Studies on the roles of deubiquitylation have been conducted in various cancers to identify the carcinogenic roles of DUBs. In this review, we evaluate the biological roles of DUBs in cancer, including proliferation, cell cycle control, apoptosis, the DNA damage response, tumor suppression, oncogenesis, and metastasis. This review mainly focuses on the regulation of different downstream effectors and pathways via biochemical regulation and posttranslational modifications. We summarize the relationship between DUBs and human cancers and discuss the potential of DUBs as therapeutic targets for cancer treatment. This review also provides basic knowledge of DUBs in the development of cancers and highlights the importance of DUBs in cancer biology.

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Section: Dubs and The Ddrmentioning

confidence: 99%

Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy

Lai

Chen

Tse

2020

IJMS

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“…Phosphorylation of OTUD5 at a single residue, Ser177, is both necessary and sufficient to activate the enzyme [7]. de Vivo et al described a new role of OTUD5 in chromatin damage response wherein the OTUD5-UBR5 (E3 ubiquitin-protein ligase UBR5) complex regulates FACT (facilitates chromatin transcription)mediated transcription as a response to DNA damage [90]. Further investigation into the nature of the interaction between OTUD5 and FACT will provide more insight into this regulation.…”

Section: Otud5mentioning

confidence: 99%

The function and regulation of OTU deubiquitinases

Sui

et al. 2019

Front. Med.

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Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including cell division, immune responses, and apoptosis. Ubiquitin-mediated control over these processes can be reversed by deubiquitinases (DUBs), which remove ubiquitin from target proteins and depolymerize polyubiquitin chains. Recently, much progress has been made in the DUBs. In humans, the ovarian tumor protease (OTU) subfamily of DUBs includes 16 members, most of which mediate cell signaling cascades. These OTUs show great variation in structure and function, which display a series of mechanistic features. In this review, we provide a comprehensive analysis of current progress in character, structure and function of OTUs, such as the substrate specificity and catalytic activity regulation. Then we discuss the relationship between some diseases and OTUs. Finally, we summarize the structure of viral OTUs and their function in immune escape and viral survival. Despite the challenges, OTUs might provide new therapeutic targets, due to their involvement in key regulatory processes.

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“…OTUD5 interacts with Ku80 to positively regulate non-homologous end joining NHEJ-mediated repair 15 . In addition, OTUD5 stabilizes SPT16 and regulates SPT16 dependent Pol II elongation 16 . In immunomodulation, TGF-β stimulation leads to excessive OTUD5 production.…”

Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Analysis of deubiquitinase OTUD5 as a biomarker and therapeutic target for cervical cancer by bioinformatic analysis (v0.1)"

2020

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OTU deubiquitinase 5 (OTUD5), as a member of the ovarian tumor protease (OTU) family, was previously reported to play important roles in DNA repair and immunity. However, little is known about its function in tumors. Cervical cancer is a malignant tumor that seriously endangers the lives of women. Here, we found that low expression of OTUD5 in cervical cancer is associated with poor prognosis. Its expression is associated with tumor stage, metastatic nodes and tumor subtypes such as those related to the phosphatidylinositol-3-kinase (PI3K)-AKT signaling, epithelial-mesenchymal transition (EMT) and hormones. In addtion, we analyzed the coexpressed genes, related miRNAs, transcription factors, kinases, E3s and interacting proteins of OTUD5. We demonstrated that OTUD5 affects the expression levels of WD repeat domain 45 (WDR45), ubiquitinspecific peptidase 11 (USP11), GRIP1 associated protein 1 (GRIPAP1) and RNA binding motif protein 10 (RBM10). Moreover, hsa-mir-137, hsa-mir-1913, hsa-mir-937, hsa-mir-607, hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5. Furthermore, we performed enrichment analysis of 22 coexpressed genes, 33 related miRNAs and 30 interacting proteins. In addition to ubiquitination and immunology related processes, they also participate in Hippo signaling, insulin signaling, EMT, histone methylation and phosphorylation kinase binding. Our study for the first time analyzed the expression of OTUD5 in cervical cancer and its relationship with clinicopathology and provided new insights for further study of its regulatory mechanism in tumors.

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The OTUD5–UBR5 complex regulates FACT-mediated transcription at damaged chromatin

Cited by 56 publications

References 53 publications

Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy

Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy

The function and regulation of OTU deubiquitinases

Peer Review #2 of "Analysis of deubiquitinase OTUD5 as a biomarker and therapeutic target for cervical cancer by bioinformatic analysis (v0.1)"

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