TFIIH interacts with the retinoic acid receptor gamma and phosphorylates its AF-1-activating domain through cdk7.
Retinoic acid receptor gamma (RARgamma) is phosphorylated in COS-1 cells at two conserved serine residues located in the N-terminal region (serines 77 and 79 in RARgamma1 and serines 66 and 68 in RARgamma2) 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 transcription/DNA repair factor TFIIH. RARgamma is more efficiently phosphorylated by TFIIH than by CAK and interacts not only with cdk7 but also with several additional subunits of TFIIH. RARgamma phosphorylation and interaction with TFIIH occur in a ligand-independent manner. Our data demonstrate also that phosphorylation of the AF-1 function modulates RARgamma transcriptional activity in a response gene-dependent manner.
Bastien
J
J
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France, BP 163, 67404 Illkirch Cedex, France.
Adam-Stitah
S
S
Riedl
T
T
Egly
J M
JM
Chambon
P
P
Rochette-Egly
C
C
D000818:Animals; D019556:COS Cells; D018844:Cyclin-Dependent Kinases; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D015398:Signal Transduction; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D015533:Transcriptional Activation; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000097768:Retinoic Acid Receptor gamma
D018844:Cyclin-Dependent Kinases; D017346:Protein Serine-Threonine Kinases; D018168:Receptors, Retinoic Acid; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000097768:Retinoic Acid Receptor gamma