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Hepatitis C virus core protein activates proteasomal activator 28 gamma to downregulate p16 levels via ubiquitin-independent proteasomal degradation.

ABSTRACT: Proteasomal activator 28 gamma (PA28γ), an essential constituent of the 20S proteasome, is frequently overexpressed in hepatocellular carcinoma. Hepatitis C virus (HCV) core protein is recently known to activate PA28γ expression in human hepatocytes via upregulation of p53 levels; however, its role in HCV tumorigenesis remains unknown. Here, we found that HCV core-activated PA28γ downregulates p16 levels via ubiquitin-independent proteasomal degradation. As a result, HCV core protein activated the Rb-E2F pathway to stimulate cell cycle progression from G₁ to S phase, resulting in an increase in cell proliferation. The potential of HCV core protein to induce these effects was almost completely abolished by either PA28γ knockdown or p16 overexpression, confirming the role of the PA28γ-mediated p16 degradation in HCV tumorigenesis.

SUBMITTER: Cha S

PROVIDER: S-EPMC7851347 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Hepatitis C virus core protein activates proteasomal activator 28 gamma to downregulate p16 levels via ubiquitin-independent proteasomal degradation.

Cha Sungkyung S Park Inbeom I Jang Kyung Lib KL

Heliyon 20210130 1

Proteasomal activator 28 gamma (PA28γ), an essential constituent of the 20S proteasome, is frequently overexpressed in hepatocellular carcinoma. Hepatitis C virus (HCV) core protein is recently known to activate PA28γ expression in human hepatocytes via upregulation of p53 levels; however, its role in HCV tumorigenesis remains unknown. Here, we found that HCV core-activated PA28γ downregulates p16 levels via ubiquitin-independent proteasomal degradation. As a result, HCV core protein activated t ...[more]

PMID: 33553768

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