Protein phosphatase 2Cbetal regulates human pregnane X receptor-mediated CYP3A4 gene expression in HepG2 liver carcinoma cells.

ABSTRACT: The human pregnane X receptor (hPXR) regulates the expression of CYP3A4, which plays a vital role in hepatic drug metabolism and has considerably reduced expression levels in proliferating hepatocytes. We have recently shown that cyclin-dependent kinase 2 (CDK2) negatively regulates hPXR-mediated CYP3A4 gene expression. CDK2 can be dephosphorylated and inactivated by protein phosphatase type 2C beta isoform long (PP2Cbetal), a unique phosphatase that was originally cloned from human liver. In this study, we sought to determine whether PP2Cbetal is involved in regulating hPXR's transactivation activity and whether PP2Cbetal affects CDK2 regulation of this activity in HepG2 liver carcinoma cells. In transactivation assays, transiently coexpressed PP2Cbetal significantly enhanced the hPXR-med

SUBMITTER: Pondugula SR 

PROVIDER: S-EPMC2939471 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature