Nuclear receptor coactivator 1 (NCOA1 (also commonly known as SRC-1))

Nuclear receptor coactivator 1 is a transcriptional coregulatory protein encoded by the NCOA1 gene. It functions primarily as a coactivator for various ligand-dependent nuclear hormone receptors—including those for steroids (estrogen receptor [ER], progesterone receptor [PGR], glucocorticoid receptor [GR]), retinoids (retinoic acid X receptors [RXRs]), thyroid hormones (thyroid hormone receptors [TRs]), and prostanoids (peroxisome proliferator–activated receptors [PPARs]). Upon activation by their respective ligands, these nuclear receptors recruit NCOA1 to DNA promoter regions where it facilitates chromatin remodeling through intrinsic histone acetyltransferase activity—making DNA more accessible for transcription machinery—and thus upregulates target gene expression. In addition to its role with classical steroid/nuclear hormone signaling pathways, it also participates in broader cellular processes including energy balance between white and brown adipose tissues and mediates responses via STAT family transcription factors. Dysregulation or altered function of NCOA1 has been implicated in cancer development/progression as well as certain metabolic disorders.

Other names

Steroid receptor coactivator 1SRC-1SRC1NCoA-1RIP160BHLHE74 (Class E basic helix-loop-helix protein 74)Protein Hin-2Renal carcinoma antigen NY-REN-52

Drugs targeting nuclear hormone receptors may indirectly affect NCOA1 activity by altering recruitment to DNA and subsequent transcriptional activation. The mechanism involves ligand-dependent recruitment of NCOA1 to activated nuclear receptors at gene promoters; this leads to chromatin remodeling through histone acetylation and increased gene expression.