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Deubiquitinase OTUD5 promotes hepatitis B virus replication by removing K48-linked ubiquitination of HBV core/precore and upregulates HNF4ɑ expressions by inhibiting the ERK1/2/mitogen-activated protein kinase pathway.
Lou, Bin; Ma, Guanghua; Yu, Xiaopeng; Lv, Feifei; Xu, Fanjie; Sun, Chengdi; Chen, Yu.
Afiliação
  • Lou B; Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Qingchun Road, Hangzhou, 310003, China.
  • Ma G; Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, 310003, China.
  • Yu X; Institute of Laboratory Medicine, Zhejiang University, Hangzhou, 310003, China.
  • Lv F; Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Qingchun Road, Hangzhou, 310003, China.
  • Xu F; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China.
  • Sun C; Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Qingchun Road, Hangzhou, 310003, China.
  • Chen Y; The Shengzhou Hospital of Traditional Chinese Medicine, Shaoxing, 312432, Zhejiang, China.
Cell Mol Life Sci ; 80(11): 336, 2023 Oct 28.
Article em En | MEDLINE | ID: mdl-37897511
ABSTRACT
Hepatitis B virus (HBV) infection is a major public health problem worldwide, causing nearly one million deaths annually. OTUD5 is a deubiquitinase associated with cancer development and innate immunity response. However, the regulatory mechanisms of OTUD5 underlying HBV replication need to be deeply elucidated. In the present investigation, we found that HBV induced significant up-regulation of OTUD5 protein in HBV-infected cells. Further study showed that OTUD5 interacted with HBV core/precore, removing their K48-linked ubiquitination chains and protecting their stability. Meanwhile, overexpression of OTUD5 could inhibit the MAPK pathway and then increase the expression of HNF4ɑ, and ERK1/2 signaling was required for OTUD5-mediated activation of HNF4α, promoting HBV replication. Together, these data indicate that OTUD5 could deubiquitinate HBV core protein degradation by its deubiquitinase function and promote HBV activity by up-regulating HNF4α expression via inhibition of the ERK1/2 pathway. These results might present a novel therapeutic strategy against HBV infection.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Vírus da Hepatite B / Hepatite B Limite: Humans Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Vírus da Hepatite B / Hepatite B Limite: Humans Idioma: En Revista: Cell Mol Life Sci Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China