Steroid receptor co-activators (SRCs) were initially described as nuclear receptor transcription co-activators, but they have recently been determined to co-regulate transcription initiated by other transcription factors. GAS is a recently identified glutamate-rich protein that interacts with SRC1, but not GRIP1 or AIB1, the other two members of the SRC family. GAS can also interact with the alpha subunit of the estrogen receptor (ERalpha), but not other receptors such as the retinoic acid receptor a, suggesting the interaction between GAS and ERalpha is relatively specific. Depletion of GAS by RNA interference in MCF7 cells led to a decrease in the mRNA and protein levels of ER target genes such as pS2, c-Myc and cyclin D1, indicating the role of GAS in the regulation of ER target genes. GAS has also been found to associate with an SET1-like methyltransferase complex specific for H3K4 methylation, suggesting that GAS has multiple roles in transcriptional regulation.
