SRC-3 transcription-coupled activation, degradation, and the ubiquitin clock: is there enough coactivator to go around in cells?
Overexpression of nuclear receptor coactivators is a frequent event in breast cancer cells and is recognized as a key mechanism for these cells to maximize their oncogenic growth state. Steroid receptor coactivator-3 [(SRC-3), also known as amplified in breast cancer-1 or AIB1] is foremost among these overexpressed oncogenic coactivators, being overexpressed in most breast cancers. Because of its oncogenic potential, normal cells must carefully control its cellular concentration. We discuss how SRC-3 quantitatively influences estrogen-regulated gene transcription when it is at limiting concentrations in normal breast cells and at nonlimiting concentrations in breast cancer cells. Precise control of the cellular concentration of SRC-3 may thus serve as a mechanism for defining growth responses to estrogen receptors and other growth-promoting transcription factors.
Lonard
David M
DM
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
O'Malley
Bert W
BW
D045744:Cell Line, Tumor; D051548:Histone Acetyltransferases / Q000502:physiology*; D006801:Humans; D056921:Nuclear Receptor Coactivator 3; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000502:physiology*
D015534:Trans-Activators; D025801:Ubiquitin; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3