Hepatitis B Virus X Protein Is Stabilized by the Deubiquitinating Enzyme VCPIP1 in a Ubiquitin-Independent Manner by Recruiting the 26S Proteasome Subunit PSMC3

Autor:	Qiong Wu, Lu Zhang, Xiazhen Xu, Yi Zhang, Jiajian Shi, Xu Lin, Wannan Chen
Rok vydání:	2022
Předmět:	Hepatitis B virus Proteasome Endopeptidase Complex Carcinoma Hepatocellular Ubiquitin Liver Neoplasms Immunology Hep G2 Cells Hepatitis B Microbiology Virology Insect Science Endopeptidases ATPases Associated with Diverse Cellular Activities Humans Viral Regulatory and Accessory Proteins
Zdroj:	Journal of Virology. 96
ISSN:	1098-5514 0022-538X
Popis:	Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, and the viral X protein (HBx) is an etiological factor in HCC development. HBx is a high-turnover protein, but knowledge of the role of deubiquitinating enzymes (DUBs) in maintaining HBx homeostasis is very limited. We used a 74-DUB library-based yeast two-hybrid assay and determined that a novel DUB, valosin-containing protein-interacting protein 1 (VCPIP1), interacted with HBx. VCPIP1 and its C-terminal amino acids 863 to 1221 upregulated the HBx protein expression, with or without HBV infection. Mechanistically, VCPIP1 stabilized HBx protein through a ubiquitin-independent pathway, which was validated by the HBx ubiquitination site mutant plasmid. Coimmunoprecipitation assays demonstrated the potency of VCPIP1 in recruiting 26S proteasome regulatory subunit 6A (PSMC3) and forming a ternary complex with HBx through mutual interaction.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91f643fd222d77a54d7475f41203e527 https://doi.org/10.1128/jvi.00611-22 Zobrazit plný text záznamu