Open AccessPhosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7
Author(s) -
Aurélia E. Lewis,
Marte Rusten,
Erling A. Høivik,
Elisabeth L. Vikse,
Magnus L. Hansson,
Annika E. Wallberg,
Marit Bakke
Publication year - 2008
Publication title -
molecular endocrinology
Language(s) - English
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2006-0478
Subject(s) - transcription factor ii h , cyclin dependent kinase 7 , biology , cyclin dependent kinase , transactivation , steroidogenic factor 1 , phosphorylation , transcription factor , microbiology and biotechnology , cyclin dependent kinase 2 , protein kinase a , biochemistry , promoter , nuclear receptor , cell cycle , gene expression , gene , cell
The nuclear receptor steroidogenic factor-1 (SF1) is critical for development and function of steroidogenic tissues. Posttranslational modifications are known to influence the transcriptional capacity of SF1, and it was previously demonstrated that serine 203 is phosphorylated. In this paper we report that serine 203 is phosphorylated by a cyclin-dependent kinase 7 (CDK7)-mediated process. As part of the CDK-activating kinase complex, CDK7 is a component of the basal transcription factor TFIIH, and phosphorylation of SF1 as well as SF1-dependent transcription was clearly reduced in cells carrying a mutation that renders the CDK-activating kinase complex unable to interact with the TFIIH core. Coimmunoprecipitation analyses revealed that SF1 and CDK7 reside in the same complex, and kinase assays demonstrated that immunoprecipitated CDK7 and purified TFIIH phosphorylate SF1 in vitro. The CDK inhibitor roscovitine blocked phosphorylation of SF1, and an inactive form of CDK7 repressed the phosphorylation level and the transactivation capacity of SF1. Structural studies have identified phosphoinositides as potential ligands for SF1. Interestingly, we found that mutations designed to block phospholipid binding dramatically decreased the level of SF1 phosphorylation. Together our results suggest a connection between ligand occupation and phosphorylation and association with the basic transcriptional machinery, indicating an intricate regulation of SF1 transactivation.