功能 |
Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.
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總結(jié) |
There are three members of the steroid?receptor co?activator (SRC) family of proteins: SRC?1 (NCoA?1), SRC?2 (TIF2/GRIP1/NCoA?2), and SRC?3 (ACTR /TRAM?1/AIB1). All?SRC family members share significant structural?homology and function to stimulate?transcription mediated by nuclear hormone receptors and other transcriptional?activators such as Stat3, NF?κB, E2F1, and p53. Two SRC proteins, SRC?1 and SRC?3, function as histone acetyltransferases. In addition, all?three family members can recruit other histone acetyltransferases (CBP/p300, PCAF) and histone methyltransferases (PRMT1, CARM1) to target promoters and cooperate to enhance expression of many genes. The SRC proteins play important roles in?multiple physiological?processes including cell proliferation, cell?survival, somatic cell?growth, mammary gland development, female reproductive function, and vasoprotection. SRC?1 and SRC?3 are conduits for kinase mediated growth factor signaling to the estrogen receptor and other transcriptional?activators. Seven SRC?1 phosphorylation sites and six SRC?3 phosphorylation sites have been identified, which are induced by steroids, cytokines, and growth factors and involve multiple kinase signaling pathways. Research has shown that all?three SRC family members are associated with increased activity of nuclear receptors in?breast, prostate, and ovarian carcinomas. According to the literature, SRC?3 is frequently amplified or overexpressed in a number of cancers, and SRC?1/PAX3 and SRC?2/MYST3 translocations are found associated with rhabdomyosarcoma?and acute myeloid leukemia, respectively.
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別名 |
NCOA1, F?SRC?1, KAT13A, MGC129719, MGC129720, NCoA?1, RIP160, SRC?1, SRC1, bHLHe42, bHLHe74, 6/G9a
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