GAS, a new glutamate-rich protein, interacts differentially with SRCs and is involved in oestrogen receptor function.

Steroid receptor coactivators (SRCs) exert profound effects on animal development and physiology. Genetic ablation experiments indicate that various SRC proteins might have differential physiological roles; however, clear evidence of functional specificity has not yet been shown at the molecular level. Here we report the identification of a new SRC1 interacting protein, glutamate-rich coactivator interacting with SRC1 (GAS), which contains a central glutamate-rich region and has transactivation activity. Interestingly, GAS interacts only with SRC1, and not with glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), the other two members of the SRC family. It interacts with oestrogen receptor-alpha (ERalpha) and participates in both oestrogen receptor-regulated gene transcription and oestrogen-stimulated G1/S cell-cycle transition. Our data thus indicate that GAS is a new transcription cofactor and that different SRCs are associated with distinct secondary cofactors.