Nuclear receptor coactivator 3 (NCOA3) (NCOA3)

Nuclear receptor coactivator 3 (NCOA3), also known as Steroid Receptor Coactivator-3 (SRC-3) or Amplified in Breast Cancer 1 (AIB1), is a critical transcriptional coactivator located at the 20q13 genomic locus (NCBI Gene ID: 8202). It functions by interacting with various nuclear receptors, such as the estrogen and androgen receptors, to facilitate the recruitment of chromatin-remodeling proteins like p300/CBP, thereby enhancing gene transcription (UniProt Q9Y6Q9). NCOA3 is characterized by its role in promoting cell proliferation, survival, and metabolic reprogramming, making it a master regulator of oncogenic pathways (PubMed: 27105312). In clinical oncology, NCOA3 is frequently overexpressed or amplified in breast, prostate, and ovarian cancers, where it correlates with poor prognosis and resistance to hormonal therapies (PubMed: 12738715). Therapeutic strategies targeting NCOA3 include small molecule inhibitors like SI-2 and MCB-613, which aim to either disrupt its protein-protein interactions or induce its degradation (PubMed: 26000477). Despite its promise, challenges remain regarding the selectivity of inhibitors across the p160 family and the potential for systemic side effects given its physiological role in development (PubMed: 21810496).

Other names

AIB1SRC-3RAC3ACTRTRAM-1p/CIPSteroid receptor coactivator 3Amplified in breast cancer 1

NCOA3 is targeted through small molecule inhibitors that block its interaction with nuclear receptors or through small molecule degraders (PROTACs or chemical degraders) that reduce its cellular concentration. Some experimental agents act as "super-stimulators" to induce proteotoxic stress and apoptosis in NCOA3-overexpressing cells.