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

作者：He, Chengyong; Qiu, Yang; Han, Peiyu; Chen, Yuanyuan; Zhang, Liyin; Yuan, Quan; Zhang, Tianying; Cheng, Tong; Yuan, Lunzhi; Huang, Chenghao; Zhang, Sheng; Yin, Zhenyu; Peng, Xian-E.; Liang, Dong; Lin, Xu; Lin, Yuchun^*; Lin, Zhongning^*; Xia, Ningshao

来源：Cell Death & Disease, 2018, 9(7): 762.

DOI：10.1038/s41419-018-0787-3

• DNA-DAMAGE
• HBX
• ACTIVATION
• PP2A
• 2A
• AP-1
• IDENTIFICATION
• PROLIFERATION
• REPLICATION
• SUPPRESSION

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 gamma and therefore affect HBx-induced hepatotoxicity? In the present study, the expression of B56 gamma 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 gamma promoted p53/p21-dependent cell cycle arrest and apoptosis. Mechanistically, B56 gamma was transactivated by AP-1, which was under the regulation of endoplasmic reticulum (ER) stress induced CREBH signaling in HBx-expressing hepatic cells. B56 gamma 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 gamma mediating cell cycle arrest and apoptosis of HBx-expressing hepatic cells and a basis for B56 gamma being a potential therapeutic target for HBV-infected hepatic cells.

• 出版日期2018-7-9
• 单位厦门大学; 福建医科大学