STEROID-RECEPTOR COACTIVATOR-1 COACTIVATES ACTIVATING PROTEIN-1-MEDIATED TRANSACTIVATIONS THROUGH INTERACTION WITH THE C-JUN AND C-FOS SUBUNITS

Steroid receptor coactivator-l (SRC-1) specifically bound to the trans cription factor AP-I subunits c-Jun and c-Fos, as demonstrated by the yeast two-hybrid tests and glutathione S-transferase pull down assays. The c-Jun and c-Fos binding sites were localized to the C-terminal su bregion of SRC-1 (amino acids 1101-1441) that encompasses the previous ly described histone acetyltransferase and receptor-binding domains. I n mammalian cells, SRC-I, similar to the previous results with CBP-p30 0 (Arias, J., Alberts, A. S., Brindle, P., Claret, F. X., Smeal, T., K arin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-229; Bannister, A. J., and Kouzarides, T. (1995) EMBO J. 14, 4758-4762), po tentiated the AP-l-mediated transactivations in a dose-dependent manne r and derepressed the mutual inhibitions between nuclear receptors and AP-1. Furthermore, coexpression of p300 further enhanced this SRC-1-p otentiated level of transactivations. Thus, we concluded that at least two distinct coactivator molecules may cooperate to regulate AP-l-dep endent transactivations and mediate transrepression between AP-I and n uclear receptors in vivo.