• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

  • Lee DK
  • Duan HO
  • Chang C

Journal

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