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The SRC-3/AIB1 coactivator is degraded in a ubiquitin- and ATP-independent manner by the REGgamma proteasome.

Steroid receptor coactivator-3 (SRC-3/AIB1) is an oncogene frequently amplified and overexpressed in breast cancers. Here we report that SRC-3 interacts with REGgamma, a proteasome activator known to stimulate the trypsin-like activity of the 20S proteasome. RNAi knockdown and gain-of-function experiments suggest that REGgamma promotes SRC-3 protein degradation. Cellular levels of REGgamma expression affect estrogen-receptor target-gene expression and cell growth as a result of its ability to promote degradation of the SRC-3 protein. In vitro proteasome proteolysis assays using purified REGgamma, SRC-3, and the 20S proteasome reinforce these conclusions and demonstrate that REGgamma promotes the degradation of SRC-3 in a ubiquitin- and ATP-independent manner. This work demonstrates the first example of a physiologically relevant endogenous cellular target for the REGgamma-proteasome complex. It also highlights the fact that an alternative mode of proteasome-mediated protein degradation, independent of the 19S proteasome regulatory cap, targets the SRC-3 protein for degradation.

Pubmed ID: 16439211


  • Li X
  • Lonard DM
  • Jung SY
  • Malovannaya A
  • Feng Q
  • Qin J
  • Tsai SY
  • Tsai MJ
  • O'Malley BW



Publication Data

January 27, 2006

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK063802-02

Mesh Terms

  • Acetyltransferases
  • Adenosine Triphosphate
  • Animals
  • Autoantigens
  • Cell Enlargement
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation
  • HeLa Cells
  • Histone Acetyltransferases
  • Humans
  • Nuclear Receptor Coactivator 3
  • Oncogene Proteins
  • Proteasome Endopeptidase Complex
  • Receptors, Estrogen
  • Trans-Activators
  • Ubiquitin
  • Up-Regulation