hSrb7, an essential human Mediator component, acts as a coactivator for the thyroid hormone receptor.
Nuclear hormone receptors interact with the basal-transcriptional complex and/or coactivators to regulate transcriptional activation. These activator-target interactions recruit the transcriptional machinery to the promoter and may also stimulate transcriptional events subsequent to the binding of the machinery to the promoter or enhancer element. We describe a novel functional interaction of the nuclear thyroid receptor (TR), with a human Mediator component (hSrb7), and a human TFIIH component (hMo15). In mammalian two-hybrid experiments as well as in GST-pull down assays, hSrb7 interacts with TR but not with other nuclear receptors such as the retinoic acid receptor (RAR) or the vitamin D receptor (VDR). Whereas hMo15 also interacts with VDR and RAR in mammalian two-hybrid assays, no association of hSrb7 with VDR or RAR is found. Accordingly, cotransfection of TR and hSrb7 increases thyroid hormone (T3)-dependent transcription in an AF-2-dependent manner, while hSrb7 causes no stimulation of vitamin D- or retinoic acid-mediated transactivation. These results reveal a novel co-activator role for hSrb7 and hMo15 on TR transcriptional responses, and demonstrate that different receptors can selectively target different co-activators or general transcription factors to stimulate transcription.
Nevado
Julián
J
Unidad de Investigación, Hospital Universitario de Getafe, 28905 Getafe, Madrid, Spain.
Tenbaum
Stephan P
SP
Aranda
Ana
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005668:Furylfuramide / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex; D018167:Receptors, Calcitriol / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D015534:Trans-Activators; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D020798:Two-Hybrid System Techniques; D014807:Vitamin D / Q000494:pharmacology; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D000970:Antineoplastic Agents; C098617:MED21 protein, human; D056892:Mediator Complex; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D015534:Trans-Activators; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D005668:Furylfuramide; D014807:Vitamin D; D051758:Transcription Factor TFIIH; D014212:Tretinoin; D005982:Glutathione Transferase; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase