Nuclear receptor coactivator 3 (NCOA3)

Nuclear receptor coactivator 3 (NCOA3) is a transcriptional coactivator that interacts with a variety of nuclear hormone receptors, including estrogen, androgen, and thyroid hormone receptors, potentiating their transcriptional activation of target genes. NCOA3 possesses intrinsic histone acetyltransferase activity, thus facilitating chromatin remodeling to enable gene activation. It is a key component of large transcriptional coactivation complexes involving p300/CBP, and its recruitment to hormone-responsive gene promoters is a central mechanism underlying steroid hormone action in multiple tissues. Overexpression, amplification, or dysregulation of NCOA3 drives oncogenic processes such as cell proliferation, tumor growth, metastasis, and therapy resistance, particularly in breast and other hormone-sensitive cancers. Beyond cancer, NCOA3 is essential for proper pluripotency maintenance in embryonic stem cells, functioning in interaction with factors such as Esrrb and the pluripotency network. NCOA3 activity is tightly regulated by posttranslational modifications, and it is increasingly recognized as a promising therapeutic target in oncology, endocrine, and regenerative medicine contexts.

Other names

Steroid receptor coactivator-3SRC-3Amplified in breast cancer 1AIB1Thyroid hormone receptor activator molecule 1TRAM-1ACTRRAC3pCIPAIB-1CTG26CAGH16KAT13BTNRC14TNRC16bHLHe42

Inhibitors (e.g., bufalin) promote NCOA3 degradation, reducing coactivation activity. Antiestrogens (e.g., tamoxifen) functionally oppose the hormone-responsive gene activation potentiated by NCOA3 overexpression (though not direct NCOA3 antagonists). Targeted modulation of posttranslational modifications (ubiquitination, methylation, phosphorylation) influences protein stability and activity.