Regulation of XPO5 phosphorylation by PP2A in hepatocellular carcinoma
Jiao Li,
Jian‐Kang Zhou,
Xiaoyu Mu,
Shu Shen,
Xiaomin Xu,
Yao Luo,
Yuxin Luo,
Yue Ming,
Yuangang Wu,
Yong Peng
Affiliations
Jiao Li
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Jian‐Kang Zhou
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Xiaoyu Mu
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Shu Shen
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Xiaomin Xu
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Yao Luo
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Yuxin Luo
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Yue Ming
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Yuangang Wu
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Yong Peng
Laboratory of Molecular Oncology Frontiers Science Center for Disease‐related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China
Abstract Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre‐miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl‐prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55β subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55β‐containing PP2A in miRNA expression and may shed light on HCC pathogenesis.
