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Cyclin D3/CDK11p58 complex is involved in the repression of androgen receptor

Hongliang Zong1, Yayun Chi, Yanlin Wang

  • 1Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Gene Research Center, Shanghai Medical College, Shanghai 200032, People's Republic of China.

Molecular and Cellular Biology
|August 19, 2007
PubMed

Insights

Cyclin D3 and CDK11p58 inhibit prostate cancer growth by repressing the androgen receptor (AR) signaling pathway. This complex phosphorylates AR, reducing its activity and hindering cancer cell proliferation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Androgen receptor (AR) is crucial for male reproductive functions and prostate cancer (PCa) development.
  • D-type cyclins are known to repress AR function, but the specific role of cyclin D3 is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which cyclin D3 represses the AR signaling pathway.
  • To investigate the interaction between cyclin D3, CDK11p58, and AR in PCa cells.

Main Methods:

  • Reporter assays in transformed cells to measure AR transcriptional activity.
  • Prostate-specific antigen (PSA) expression analysis in PCa cells.
  • In vitro and in vivo phosphorylation assays.
  • Cell proliferation assays.

Main Results:

  • Cyclin D3 and CDK11p58 were found to repress AR transcriptional activity and PSA expression.
  • A ternary complex of AR, cyclin D3, and CDK11p58 was identified and localized in the prostate.
  • Cyclin D3/CDK11p58 complex phosphorylates AR at Ser-308, inhibiting its transcriptional activation unit 1 (TAU1).
  • Androgen-dependent PCa cell proliferation was inhibited by cyclin D3/CDK11p58 via AR repression.

Conclusions:

  • Cyclin D3 and CDK11p58 form a complex that negatively regulates AR function.
  • This cyclin D3/CDK11p58 signaling pathway represents a potential therapeutic target for prostate cancer.

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