Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation.

Abstract

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.

• Authors: D K Lee, H O Duan, C Chang
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 13 Pg. 9978-84 (Mar 30 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11266437 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enzyme Inhibitors
• Ligands
• Receptors, Androgen
• Transcription Factors
• Transcription Factors, TFII
• Transcription Factor TFIIH
• Dichlororibofuranosylbenzimidazole
• Positive Transcriptional Elongation Factor B
• Protein Serine-Threonine Kinases
• CDK9 protein, human
• Cyclin-Dependent Kinase 9
• Cyclin-Dependent Kinases
• Prostate-Specific Antigen

Topics

• Cell Line
• Cell Nucleus (metabolism)
• Cyclin-Dependent Kinase 9
• Cyclin-Dependent Kinases (metabolism)
• Dichlororibofuranosylbenzimidazole (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Humans
• Ligands
• Male
• Models, Biological
• Mutation
• Plasmids (metabolism)
• Positive Transcriptional Elongation Factor B
• Precipitin Tests
• Prostate-Specific Antigen (genetics)
• Prostatic Neoplasms (metabolism)
• Protein Binding
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Protein Structure, Tertiary
• Receptors, Androgen (metabolism)
• Transcription Factor TFIIH
• Transcription Factors (metabolism)
• Transcription Factors, TFII
• Transcription, Genetic
• Transcriptional Activation
• Transfection
• Tumor Cells, Cultured