Nuclear receptor coactivator 3
protein-coding gene in the species Homo sapiens
The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is also frequently called 'amplified in breast 1' (AIB1), steroid receptor coactivator-3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1).
Function
NCOA3 is a transcriptional coactivator protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA3 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA3, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA3 assists nuclear receptors in the upregulation of gene expression.
Clinical significance
The ratio of PAX2 to AIB-1 protein expression may be predictive of the effectiveness of tamoxifen in breast cancer treatment.
Several molecular mechanisms implicate NCOA3 (AIB1) in the endocrine therapy resistance (depicted in the figure). Signaling pathways or mutations (i.e. HER2/neu overexpression, activating mutations in PIK3CA (PI3K), activating mutations in the proto-oncogene tyrosine-protein kinase Src, etc.) that lead to persistent activation of ERK and/or PIK3CA/AKT kinase pathways result, in one hand in an enhanced AIB1 transcriptional coactivation capacity, and in the other hand in the inhibition of the proteasome-dependent AIB1 turn-over and therefore, in AIB1 overexpression.
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