USP24 is an ISG15 cross-reactive deubiquitinase that mediates IFN-I production by de-ISGylating the RNA helicase MOV10 DOI Creative Commons
Rishov Mukhopadhyay, Simeon D. Draganov, Jimmy J.L.L. Akkermans

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 6, 2024

ABSTRACT The interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier induced by type I Interferon (IFN-I) and plays crucial role in the innate immune response against viral infections. ISG15 conjugated to target proteins an enzymatic cascade through process called ISGylation. While ubiquitin-specific protease 18 (USP18) well-defined deISGylase counteracting conjugation, cross-reactive deubiquitylating enzymes (DUBs) have also been reported. Our study reports USP24 as novel DUB identified activity-based protein profiling (ABPP). We demonstrate that recombinant processed pro-ISG15 ISG15-linked synthetic substrates vitro . Moreover, depletion of significantly increased accumulation conjugates upon IFN-β stimulation. An extensive proteomic analysis USP24-dependent ISGylome, integrating total proteome, GG-peptidome, interactome data, helicase Moloney leukemia virus 10 (MOV10) specific for deISGylation. Further validation cells revealed ISGylated MOV10 enhances production/secretion, whereas deISGylates negatively regulate response. This showcases USP24’s roles modulating ISGylation modulation IFN-I-dependent responses, with potential therapeutic implications infectious diseases, cancer, autoimmunity, neuroinflammation.

Язык: Английский

USP24 promotes hepatocellular carcinoma tumorigenesis through deubiquitinating and stabilizing TRAF2 DOI Creative Commons
Nana Zhou, Chaoqin Guo, Xiangyu Li

и другие.

Biochemical Pharmacology, Год журнала: 2024, Номер 229, С. 116473 - 116473

Опубликована: Авг. 9, 2024

Ubiquitin-specific peptidase 24 (USP24), a member of the deubiquitinase family, plays an important role in tumor regulation. However, USP24 Hepatocellular carcinoma（HCC）is unknown. The aim our study was to explore HCC seek new therapeutic targets for HCC. In this study, we found that aberrantly upregulated tissues and predicted poor prognosis. markedly promoted proliferation progression vitro vivo. Mechanistically, binds necrosis factor receptor-associated 2(TRAF2) inhibits its degradation, thereby promoting accumulation TRAF2. Upregulation TRAF2 activated protein kinase B/nuclear kappa-B (AKT/ NF-κB) signaling pathway cell survival. addition, positively correlated with programmed death ligand 1(PD-L1) expression HCC, highlighting clinical significance activation immune evasion. Deletion enhanced tumor-killing ability CD8

Язык: Английский

Процитировано

6
USP24 promotes hepatocellular carcinoma progression by deubiquitinating and stabilizing YAP1 DOI Creative Commons

Huizhuang Shan,

Jiaguo Yuan,

Lei Xian

и другие.

Cancer Cell International, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 26, 2025

Yes-associated protein 1 (YAP1) plays a pivotal role in promoting the progression of hepatocellular carcinoma (HCC). Emerging evidence shows that inducing YAP1 degradation represents promising strategy. Here, we identified USP24 as bona fide deubiquitinating enzyme for YAP1. directly interacts with and deubiquitinates YAP1, thereby stabilizing levels. Clinically, was significantly upregulated HCC tissues correlated poor patient prognosis. Depletion suppressed proliferation cells vitro, which could be rescued by restoration Consistent these findings, knockdown inhibited tumor growth xenograft mouse model. Overall, our study reveals USP24/YAP1 axis critical malignant HCC, thus providing rationale potential therapeutic interventions YAP1-driven HCC.

Язык: Английский

Процитировано

0
USP24 is an ISG15 cross-reactive deubiquitinase that mediates IFN-I production by de-ISGylating the RNA helicase MOV10 DOI Creative Commons
Rishov Mukhopadhyay, Simeon D. Draganov, Jimmy J.L.L. Akkermans

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 6, 2024

ABSTRACT The interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier induced by type I Interferon (IFN-I) and plays crucial role in the innate immune response against viral infections. ISG15 conjugated to target proteins an enzymatic cascade through process called ISGylation. While ubiquitin-specific protease 18 (USP18) well-defined deISGylase counteracting conjugation, cross-reactive deubiquitylating enzymes (DUBs) have also been reported. Our study reports USP24 as novel DUB identified activity-based protein profiling (ABPP). We demonstrate that recombinant processed pro-ISG15 ISG15-linked synthetic substrates vitro . Moreover, depletion of significantly increased accumulation conjugates upon IFN-β stimulation. An extensive proteomic analysis USP24-dependent ISGylome, integrating total proteome, GG-peptidome, interactome data, helicase Moloney leukemia virus 10 (MOV10) specific for deISGylation. Further validation cells revealed ISGylated MOV10 enhances production/secretion, whereas deISGylates negatively regulate response. This showcases USP24’s roles modulating ISGylation modulation IFN-I-dependent responses, with potential therapeutic implications infectious diseases, cancer, autoimmunity, neuroinflammation.

Язык: Английский

Процитировано

0