Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation.
Androgen receptor (AR) may communicate with the general transcription machinery on the core promoter to exert its function as a transcriptional modulator. Our previous report demonstrated that the AR interacted with transcription factor IIH (TFIIH) under physiological conditions and that overexpression of Cdk-activating kinase, the kinase moiety of TFIIH, enhanced AR-mediated transcription in prostate cancer cells. In an effort to further dissect the mechanisms implicated in AR transactivation, we report here that AR interacts with PITALRE, a kinase subunit of positive elongation factor b (P-TEFb). Cotransfection of the plasmid encoding the mutant PITALRE (mtPITALRE), defective in its RNA polymerase II COOH-terminal domain (CTD)-kinase activity, resulted in preferential inhibition of AR-mediated transactivation. Indeed, AR transactivation in PC-3 cells was preferentially inhibited at the low concentration of 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), a CTD kinase inhibitor. These results suggest that CTD phosphorylation may play an important role in AR-mediated transcription. Furthermore, a nuclear run-on transcription assay of the prostate-specific antigen gene, an androgen-inducible gene, showed that transcription efficiency of the distal region of the gene was enhanced upon androgen induction. Taken together, our reports suggest that AR interacts with TFIIH and P-TEFb and enhances the elongation stage of transcription.
Pubmed ID: 11266437 RIS Download
Cell Line | Cell Nucleus | Cyclin-Dependent Kinase 9 | Cyclin-Dependent Kinases | Dichlororibofuranosylbenzimidazole | Enzyme Inhibitors | Humans | Ligands | Male | Models, Biological | Mutation | Plasmids | Positive Transcriptional Elongation Factor B | Precipitin Tests | Prostate-Specific Antigen | Prostatic Neoplasms | Protein Binding | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Receptors, Androgen | Transcription Factor TFIIH | Transcription Factors | Transcription Factors, TFII | Transcription, Genetic | Transcriptional Activation | Transfection | Tumor Cells, Cultured