OTUD5 cooperates with TRIM25 in transcriptional regulation and tumor progression via deubiquitination activity.
Animals
Cell Line, Tumor
Cell Proliferation
/ genetics
DNA-Binding Proteins
/ genetics
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Genetic Predisposition to Disease
/ genetics
HEK293 Cells
Heterografts
Humans
Lung Neoplasms
/ genetics
Male
Mice
Mice, Knockout
Mice, Nude
Middle Aged
Ovarian Neoplasms
/ genetics
RNA Interference
Signal Transduction
Transcription Factors
/ genetics
Transcriptome
Ubiquitin-Specific Proteases
/ genetics
Ubiquitination
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 08 2020
21 08 2020
Historique:
received:
07
08
2019
accepted:
20
07
2020
entrez:
23
8
2020
pubmed:
23
8
2020
medline:
15
9
2020
Statut:
epublish
Résumé
Oncogenic processes exert their greatest effect by targeting regulators of cell proliferation. Studying the mechanism underlying growth augmentation is expected to improve clinical therapies. The ovarian tumor (OTU) subfamily deubiquitinases have been implicated in the regulation of critical cell-signaling cascades, but most OTUs functions remain to be investigated. Through an unbiased RNAi screen, knockdown of OTUD5 is shown to significantly accelerate cell growth. Further investigation reveals that OTUD5 depletion leads to the enhanced transcriptional activity of TRIM25 and the inhibited expression of PML by altering the ubiquitination level of TRIM25. Importantly, OTUD5 knockdown accelerates tumor growth in a nude mouse model. OTUD5 expression is markedly downregulated in tumor tissues. The reduced OTUD5 level is associated with an aggressive phenotype and a poor clinical outcome for cancers patients. Our findings reveal a mechanism whereby OTUD5 regulates gene transcription and suppresses tumorigenesis by deubiquitinating TRIM25, providing a potential target for oncotherapy.
Identifiants
pubmed: 32826889
doi: 10.1038/s41467-020-17926-7
pii: 10.1038/s41467-020-17926-7
pmc: PMC7442798
doi:
Substances chimiques
DNA-Binding Proteins
0
Transcription Factors
0
Trim25 protein, mouse
0
Otud5 protein, mouse
EC 3.4.19.12
Ubiquitin-Specific Proteases
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4184Références
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