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.