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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


  • Lee DK
  • Duan HO
  • Chang C


The Journal of biological chemistry

Publication Data

March 30, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: CA55639
  • Agency: NCI NIH HHS, Id: CA71570

Mesh Terms

  • 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