A novel steroid receptor coactivator-3 (SRC-3), a coactivator of steroid nuclear receptor transcription was cloned and characterized. SRC-3 represents a new member of a family of steroid receptor coactivators that includes TAF-1 and TIF-2. SRC-3 demonstrated selective nuclear receptor-stimulated gene transcription in a ligand-dependent manner. Protein-protein interaction assays, including BIACORE analyses, demonstrated that the interaction between SRC-3 and ER a was much stronger than that observed for SRC-3 and ER b. An intrinsic transactivation function was observed in the C-terminal half of SRC-3. SRC-3 was differentially expressed in various tissues and, among several tumor cells examined, was most abundant in the nuclear fraction of MCF-7 breast cancer cells. Therefore, SRC-3 is a third member of a family of steroid receptor coactivators that has a distinct tissue distribution and intriguing selectivity between ER a and ER b.
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