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Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor

Young-Hwa Goo1, Soon-Young Na, Hao Zhang

  • 1Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

The Journal of Biological Chemistry
|December 3, 2003
PubMed

Insights

Activating signal cointegrator-2 (ASC-2) interacts with the androgen receptor (AR) indirectly, with retinoblastoma (Rb) potentially mediating this interaction. ASC-2 demonstrates multiple nuclear receptor interaction domains, including a novel one for AR.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Activating signal cointegrator-2 (ASC-2) is a cancer-amplified coactivator for nuclear receptors.
  • ASC-2 possesses two known LXXLL motifs for nuclear receptor interaction.
  • Androgen receptor (AR) is a key nuclear receptor implicated in various cellular processes.

Purpose of the Study:

  • To investigate the interaction between ASC-2 and androgen receptor (AR).
  • To identify novel binding sites and mechanisms of ASC-2-mediated AR transactivation.
  • To explore the role of retinoblastoma (Rb) in the ASC-2 and AR interaction.

Main Methods:

  • Co-transfection assays in HeLa and Rb-null Saos2 cells.
  • Analysis of ASC-2 interaction interfaces with AR and Rb.
  • Investigating the effect of ectopic Rb expression on ASC-2-mediated AR transactivation.

Main Results:

  • ASC-2 exhibits an indirect binding site for AR, separate from its LXXLL motifs.
  • This AR binding region on ASC-2 overlaps with its direct interaction interface for Rb.
  • Retinoblastoma (Rb) expression facilitates ASC-2's coactivation of AR in Rb-null cells.

Conclusions:

  • ASC-2 contains at least three distinct nuclear receptor interaction domains.
  • The interaction between ASC-2 and AR in vivo may be mediated by Rb.
  • This suggests a complex regulatory mechanism for AR transactivation involving ASC-2 and Rb.

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