Staying the distance: avoiding the proteasomal trap.
There are a multitude of nuclear receptor coactivators, and as a result, individual constituents of activation complexes are often overlooked when studying the specific actions of hormone signaling pathways. Specificity is typically associated with the receptor and its cognate ligand. However, SRC-3 has distinguished itself by persistent association with cell growth. In the February 29 issue of Molecular Cell, Yi et al. demonstrate that estrogen-induced posttranslational modulation of SRC-3 by atypical PKC shields it from proteasomal degradation, facilitating increased estrogenic gene activity. This process may have important implications in different types of hormone-sensitive tumors, particularly breast cancer.
Downes
Michael
M
Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 Torrey Pines Road, La Jolla, CA 92037, USA.
Evans
Ronald M
RM
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056921:Nuclear Receptor Coactivator 3; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
D004967:Estrogens; D011960:Receptors, Estrogen; D015534:Trans-Activators; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; C115015:PKC-3 protein; D011493:Protein Kinase C; D046988:Proteasome Endopeptidase Complex