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ER stress regulating protein phosphatase 2A-B56?, targeted by hepatitis B virus X protein, induces cell cycle arrest and apoptosis of hepatocytes.


ABSTRACT: Hepatitis B virus X (HBx) protein contributes to the progression of hepatitis B virus (HBV)-related hepatic injury and diseases, but the exact mechanism remains unclear. Protein phosphatase 2?A (PP2A) is a major serine/threonine phosphatase involved in regulating many cellular phosphorylation signals that are important for regulation of cell cycle and apoptosis. Does HBx target to PP2A-B56? and therefore affect HBx-induced hepatotoxicity? In the present study, the expression of B56? positively correlated with the level of HBx in HBV-infected primary human hepatocytes in human-liver-chimeric mice, HBx-transgenic mice, HBV-infected cells, and HBx-expressing hepatic cells. B56? promoted p53/p21-dependent cell cycle arrest and apoptosis. Mechanistically, B56? was transactivated by AP-1, which was under the regulation of endoplasmic reticulum (ER) stress induced CREBH signaling in HBx-expressing hepatic cells. B56? dephosphorylated p-Thr55-p53 to trigger p53/p21 pathway-dependent cell cycle G1 phase arrest, resulting in apoptosis of hepatic cells. In conclusion, this study provides a novel insight into a mechanism of B56? mediating cell cycle arrest and apoptosis of HBx-expressing hepatic cells and a basis for B56? being a potential therapeutic target for HBV-infected hepatic cells.

SUBMITTER: He C 

PROVIDER: S-EPMC6037732 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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ER stress regulating protein phosphatase 2A-B56γ, targeted by hepatitis B virus X protein, induces cell cycle arrest and apoptosis of hepatocytes.

He Chengyong C   Qiu Yang Y   Han Peiyu P   Chen Yuanyuan Y   Zhang Liyin L   Yuan Quan Q   Zhang Tianying T   Cheng Tong T   Yuan Lunzhi L   Huang Chenghao C   Zhang Sheng S   Yin Zhenyu Z   Peng Xian-E XE   Liang Dong D   Lin Xu X   Lin Yuchun Y   Lin Zhongning Z   Xia Ningshao N  

Cell death & disease 20180709 7


Hepatitis B virus X (HBx) protein contributes to the progression of hepatitis B virus (HBV)-related hepatic injury and diseases, but the exact mechanism remains unclear. Protein phosphatase 2 A (PP2A) is a major serine/threonine phosphatase involved in regulating many cellular phosphorylation signals that are important for regulation of cell cycle and apoptosis. Does HBx target to PP2A-B56γ and therefore affect HBx-induced hepatotoxicity? In the present study, the expression of B56γ positively c  ...[more]

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