sRC1

SRC-1, or steroid receptor coactivator-1, is a transcriptional coactivator belonging to the p160/SRC family. It is encoded by the NCOA1 gene and functions to enhance the activity of multiple nuclear hormone receptors and other transcription factors. SRC-1 facilitates ligand-dependent transcription by binding receptor proteins through conserved LxxLL motifs and recruiting additional coactivators and chromatin-modifying enzymes, such as CBP/p300 and components of the Mediator complex. This leads to chromatin remodeling and the assembly of transcriptional machinery at target gene promoters.

SRC-1 interacts with a broad range of receptors, including estrogen receptors, androgen receptor, glucocorticoid receptor, thyroid hormone receptor, retinoic acid receptors, and peroxisome proliferator-activated receptors. Through these interactions, SRC-1 influences diverse biological processes, including development, metabolism, reproductive physiology, and brain function. It is widely expressed, with varying levels across tissues such as the mammary gland, adipose tissue, and the central nervous system.

In a clinical context, SRC-1 has been studied for its role in hormone-dependent cancers, particularly estrogen receptor–positive breast cancer, where altered expression or activity can affect tumor growth and treatment response. Because SRC-1 can function redundantly with closely related coactivators SRC-2 and SRC-3, the full impact of SRC-1 depends on cellular context and the presence of other coactivators.

SRC-1 can be produced as multiple isoforms through alternative splicing. It is one of several coactivators that shape transcriptional outcomes by modulating chromatin structure and facilitating access of transcriptional machinery to target genes. Related genes include NCOA2 and NCOA3, which encode SRC-2 and SRC-3, respectively.