SRC1NCOA1

SRC1NCOA1 is the designation used for the steroid receptor coactivator-1 (SRC-1), also known as nuclear receptor coactivator 1 (NCOA1). In humans, the NCOA1 gene encodes the SRC-1 protein, a member of the p160 family of transcriptional coactivators essential for efficient transcription of many steroid receptor target genes. SRC-1 functions as a scaffold that bridges nuclear hormone receptor complexes to the general transcription machinery and chromatin-modifying enzymes.

Mechanism and interactions: SRC-1 binds to ligand-activated nuclear receptors through conserved NR boxes containing LXXLL motifs, enabling recruitment of histone acetyltransferases such as CBP/p300 and other coactivators. This promotes chromatin remodeling and enhanced RNA polymerase II–mediated transcription. SRC-1 interacts with estrogen receptors, androgen receptors, progesterone receptors, and other transcription factors, and can cooperate with related coactivators SRC-2 (NCOA2) and SRC-3 (NCOA3) in overlapping regulatory networks.

Structure and regulation: The protein contains activation domains and receptor-interaction motifs that mediate contact with transcriptional and chromatin-modifying machinery. Alternative splicing and post-translational modifications generate multiple isoforms with distinct regulatory properties, allowing context-specific modulation of receptor signaling.

Clinical relevance: Abnormal expression or activity of SRC-1/NCOA1 has been reported in hormone-dependent cancers, including breast cancer, where it can modulate estrogen receptor signaling and influence therapeutic responses. It remains a focus of research as a potential biomarker or therapeutic target.

Evolution and nomenclature: SRC-1/NCOA1 is conserved across vertebrates, with orthologs in mouse and other mammals. The SRC-1 designation reflects its identity as nuclear receptor coactivator-1, a key coactivator in steroid receptor signaling.