Open AccessRegulation of XPO5 phosphorylation by PP2A in hepatocellular carcinoma
Author(s) -
Li Jiao,
Zhou JianKang,
Mu Xiaoyu,
Shen Shu,
Xu Xiaomin,
Luo Yao,
Luo Yuxin,
Ming Yue,
Wu Yuangang,
Peng Yong
Publication year - 2022
Publication title -
medcomm
Language(s) - English
Resource type - Journals
ISSN - 2688-2663
DOI - 10.1002/mco2.125
Subject(s) - dephosphorylation , protein phosphatase 2 , phosphorylation , protein subunit , phosphatase , cytoplasm , kinase , microbiology and biotechnology , biology , hepatocellular carcinoma , chemistry , biochemistry , cancer research , gene
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.