CDK8/19 inhibition induces premature G1/S transition and ATR-dependent cell death in prostate cancer cells.

ABSTRACT: The CDK8/19 kinase module comprises a subcomplex that interacts with the Mediator complex and regulates gene expression through phosphorylation of transcription factors and Mediator subunits. Mediator complex subunits have been increasingly implicated in cancer and other diseases. Although high expression of CDK8/19 has been demonstrated in prostate cancer, its function has not been thoroughly examined. Here we report that CDK8/19 modulates the gene expression of cell cycle regulators and thereby maintains the proper G1/S transition in prostate cancer cells. We show that highly selective CDK8/19 inhibitors exerted anti-proliferative activity in prostate cancer cells both in vitro and in vivo. In CDK8/19 inhibitor-sensitive prostate cancer cells, the compounds reduced the popu

SUBMITTER: Nakamura A 

PROVIDER: S-EPMC5862592 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature