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Atypical protein kinase C regulates dual pathways for degradation of the oncogenic coactivator SRC-3/AIB1

Ping Yi1, Qin Feng, Larbi Amazit

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Molecular Cell
|March 4, 2008
PubMed

Insights

Atypical protein kinase C (aPKC) stabilizes Steroid Receptor Coactivator-3 (SRC-3) by preventing its degradation. This discovery reveals a new mechanism for controlling SRC-3 levels in cancer cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Steroid Receptor Coactivator-3 (SRC-3) is a potent growth promoter implicated in tumorigenesis.
  • SRC-3 levels are regulated by proteasomal degradation pathways.
  • Atypical protein kinase C (aPKC) is often overexpressed in various cancers.

Purpose of the Study:

  • To investigate the role of aPKC in regulating SRC-3 protein stability.
  • To elucidate the mechanism by which aPKC affects SRC-3 levels.

Main Methods:

  • Phosphorylation assays to determine aPKC's effect on SRC-3.
  • Analysis of SRC-3 interaction with the 20S core proteasome.
  • Site-directed mutagenesis to identify key regions in SRC-3.

Main Results:

  • aPKC phosphorylates and stabilizes SRC-3 in an Estrogen Receptor (ER)-dependent manner.
  • An acidic residue-rich region in SRC-3 is crucial for aPKC-mediated stabilization.
  • aPKC reduces SRC-3 interaction with the C8 subunit of the 20S proteasome, inhibiting degradation.

Conclusions:

  • aPKC-mediated phosphorylation of SRC-3 inhibits its proteasomal degradation.
  • This signaling pathway provides a novel mechanism for controlling SRC-3 levels.
  • Targeting this interaction could offer new therapeutic strategies for cancers with SRC-3 overexpression.

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