A TATA binding protein-associated factor functions as a coactivator for thyroid hormone receptors.
Transcriptional regulation by thyroid hormone receptors (TRs) requires the TR to interact with various proteins. The TATA binding protein-associated factors (TAFs) are cofactors for several transcription factors and, therefore, are candidate cofactors for the TR. To determine whether one or more of the TAFs are cofactors for TRs, direct protein interactions between human TR beta and several Drosophila TAFs were quantitated in vitro. The human (h) TR beta bound specifically to dTAFII110 and weakly to dTAFII60, but did not bind to dTAFII30 alpha, dTAFII30 beta, dTAFII40, dTAFII80, or dTAFII150. The dTAFII110:hTR beta interaction required the carboxyl-terminals of both proteins. The dTAFII110 also interacted with the hTR alpha 1 carboxyl-terminus in a yeast two-hybrid system. Thyroid hormone destabilized the dTAFII110:TR interaction in vitro, but had no effect on the interaction in the two-hybrid system. The dTAFII110 did not bind to human retinoid X receptor alpha in vitro, indicating that this TAF interacts differentially with nuclear receptors. The transcriptional function of hTR beta was enhanced by dTAFII110 in transfection assays, indicating that this TAF can function in the thyroid hormone signalling pathway. Thus, TAFII110 functions as a cofactor for TRs, and the interactions between specific TAFs and nuclear receptors may provide another level of selectivity for transcriptional responses to hormones.
Petty
K J
KJ
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857, USA. petty01@utsw.swmed.edu
Krimkevich
Y I
YI
Thomas
D
D
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D029721:Drosophila Proteins; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D013963:Thyroid Hormones / Q000378:metabolism / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; C486319:TAF1C protein, human; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D013963:Thyroid Hormones; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors