NCOA3
Description
The NCOA3 (nuclear receptor coactivator 3) is a protein-coding gene located on chromosome 20.
NCOA3, also known as amplified in breast 1 (AIB1), steroid receptor coactivator-3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1), is a protein encoded by the NCOA3 gene in humans. It is a transcriptional coactivator protein containing several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA3 is recruited to DNA promoter sites by ligand-activated nuclear receptors. It then acylates histones, making downstream DNA more accessible to transcription, thereby assisting nuclear receptors in upregulating gene expression. The ratio of PAX2 to AIB-1 protein expression may predict the effectiveness of tamoxifen in breast cancer treatment. Several molecular mechanisms implicate NCOA3 (AIB1) in endocrine therapy resistance. Signaling pathways or mutations, such as HER2/neu overexpression, activating mutations in PIK3CA (PI3K), or activating mutations in the proto-oncogene tyrosine-protein kinase Src, lead to persistent activation of ERK and/or PIK3CA/AKT kinase pathways. These pathways enhance AIB1 transcriptional coactivation capacity and inhibit proteasome-dependent AIB1 turn-over, resulting in AIB1 overexpression.
NCOA3 is a nuclear receptor coactivator that directly binds to nuclear receptors and stimulates their transcriptional activity in a hormone-dependent manner. It forms a multisubunit coactivator complex, likely through chromatin remodeling. NCOA3 participates in the coactivation of various nuclear receptors, including those for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR), and prostanoids (PPARs). It possesses histone acetyltransferase activity and is also involved in the coactivation of the NF-kappa-B pathway through interaction with the NFKB1 subunit.
NCOA3 is also known as ACTR, AIB-1, AIB1, CAGH16, CTG26, KAT13B, RAC3, SRC-3, SRC3, TNRC14, TNRC16, TRAM-1, bHLHe42, pCIP.
