This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lewis, A. E. Articles by Bakke, M. Search for Related Content PubMed PubMed Citation Articles by Lewis, A. E. Articles by Bakke, M.

Phosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7

Department of Biomedicine (A.E.L., M.R., E.A.H., E.L.V., M.B.), University of Bergen, 5009 Bergen, Norway; and Department of Biosciences and Nutrition (M.L.H., A.E.W.), Karolinska Institutet, 141 86 Stockholm, Sweden

Address all correspondence and requests for reprints to: Marit Bakke, Department of Biomedicine, University of Bergen, Jonas Lies vei 9, 5009 Bergen, Norway, E-mail: Marit.Bakke{at}biomed.uib.no.

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.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1

Coregulators:   CDK7  |  MAT1