SRC3

SRC-3, or steroid receptor coactivator-3, is a member of the p160 family of nuclear receptor coactivators. It is encoded by the NCOA3 gene in humans and is also known by aliases such as AIB1 and SRC-3. The protein is large and modular, containing activation domains AD1, AD2, AD3 and receptor-interacting LXXLL motifs that enable binding to steroid receptors and other transcription factors.

As a coactivator, SRC-3 bridges nuclear receptors to chromatin-modifying enzymes, promoting histone acetylation and remodeling by recruiting CBP/p300, PCAF, and related factors. It enhances transcriptional responses to hormones such as estrogens, androgens, and progestins, as well as signaling pathways converging on transcription factors such as NF-κB and AP-1.

SRC-3 is widely expressed, with high levels in mammary tissue. Genetic amplification and overexpression of NCOA3 have been observed in breast cancers and are associated with increased hormone signaling, tumor growth, and poorer prognosis. The activity of SRC-3 is regulated by post-translational modifications, including phosphorylation and ubiquitination, which influence stability and coactivator efficiency.

Because of its role in hormone signaling and chromatin regulation, SRC-3 is studied as a potential therapeutic target in hormone-driven cancers. Research continues to elucidate its full range of interaction partners and context-dependent functions.

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