TFIIH interacts with the retinoic acid receptor γ and phosphorylates its AF-1-activating domain through cdk7

Abstract

Retinoic acid receptor γ (RARγ) is phosphorylated in COS-1 cells at two conserved serine residues located in the N-terminal region (serines 77 and 79 in RARγ1 and serines 66 and 68 in RARγ2) that contains the activation function AF-1. These serines are phosphorylated in vitro by cdk7, a cyclin-dependent kinase associated to cyclin H and MAT1 in the CAK complex (cdk7·cyclin H·MAT1), that is found either free or as a component of the tran- scription/DNA repair factor TFIIH. RARγ is more efficiently phosphorylated by TFIIH than by CAK and interacts not only with cdk7 but also with several additional subunits of TFIIH. RARγ phosphorylation and interaction with TFIIH occur in a ligand-independent manner. Our data demonstrate also that phosphorylation of the AF-1 function modulates RARγ transcriptional activity in a response gene-dependent manner.