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

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
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.
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
Cell Jan. 27, 2006; 124(2);381-92 [PUBMED:16439211]
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