mTORC1 down-regulates cyclin-dependent kinase 8 (CDK8) and cyclin C (CycC)

Daorong Feng, Dou Yeon Youn, Xiaoping Zhao, Yanguang Gao, William J. Quinn, Alus M. Xiaoli, Yan Sun, Morris J. Birnbaum, Jeffrey E. Pessin, Fajun Yang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

In non-alcoholic fatty liver disease (NAFLD) and insulin resistance, hepatic de novo lipogenesis is often elevated, but the underlying mechanisms remain poorly understood. Recently, we show that CDK8 functions to suppress de novo lipogenesis. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a critical regulator of CDK8 and its activating partner CycC. Using pharmacologic and genetic approaches, we show that increased mTORC1 activation causes the reduction of the CDK8-CycC complex in vitro and in mouse liver in vivo. In addition, mTORC1 is more active in three mouse models of NAFLD, correlated with the lower abundance of the CDK8-CycC complex. Consistent with the inhibitory role of CDK8 on de novo lipogenesis, nuclear SREBP-1c proteins and lipogenic enzymes are accumulated in NAFLD models. Thus, our results suggest that mTORC1 activation in NAFLD and insulin resistance results in down-regulation of the CDK8-CycC complex and elevation of lipogenic protein expression.

Original languageEnglish (US)
Article numbere0126240
JournalPloS one
Volume10
Issue number6
DOIs
StatePublished - Jun 4 2015

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

Fingerprint

Dive into the research topics of 'mTORC1 down-regulates cyclin-dependent kinase 8 (CDK8) and cyclin C (CycC)'. Together they form a unique fingerprint.

Cite this