From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator.
The androgen receptor (AR), like other steroid receptors, modulates the activity of the general transcription machinery on the core promoter to exert its function as a regulator. Co-immunoprecipitation of prostate cancer LNCaP cell extract using protein A-Sepharose coupled with anti-AR antibody indicates that the AR interacts with the general transcription factor TFIIH in a physiological condition. Co-transfection of cdk activating kinase (CAK), the kinase moiety of TFIIH, enhanced AR-mediated transcription in a ligand-dependent manner in human prostate cancer PC-3 and LNCaP cells, and in a ligand-independent manner in human prostate cancer DU145 cells. Detailed interaction studies further revealed that the AR NH(2)-terminal domain interacting with CAK was essential for the CAK-induced AR transactivation. Together, our data suggest that the AR may interact with TFIIH for efficient communication with the general transcription factors/RNA polymerase II on the core promoter.
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George Whipple Laboratory for Cancer Research, Department of Pathology, Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
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Chang
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D056748:Cyclin H; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII; D014407:Tumor Cells, Cultured; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C490039:TAF6 protein, S cerevisiae; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase