This entry represents the SH2 domain of STAT5b.STAT5 is a member of the STAT family of transcription factors. Two highly related proteins, STAT5a and STAT5b are encoded by separate genes, but are 90% identical at the amino acid level. Both STAT5a and STAT5b are ubiquitously expressed and functionally interchangeable. They regulate B and T cell development [, ].STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins []. Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes []. STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 [].
STAT5 is a member of the STAT family of transcription factors. Two highly related proteins, STAT5a and STAT5b are encoded by separate genes, but are 90% identical at the amino acid level. Both STAT5a and STAT5b are ubiquitously expressed and functionally interchangeable. They regulate B and T cell development [, ].STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins []. Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes []. STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 [].
Nuclear receptor coactivator 1 (NCOA1, also known as SRC-1) belongs to the SRC/p160 nuclear receptor coactivator family, which contains proteins that are ligand-dependent transcription factors []. These receptors can function as molecular switches [].NCOA1 directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion []. It is involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs) []. It is also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors [, , ]. It 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 []. It can be regulated by sumoylation and ubiquitination [].
This group represents the nuclear receptor coactivator family, also known as the SRC/p160 nuclear receptor coactivator family, which contains proteins that are ligand-dependent transcription factors []. These receptors can function as molecular switches [].NCOA1 directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion []. It is involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs) []. It is also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors [, , ]. It 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 []. It can be regulated by sumoylation and ubiquitination []. NCOA2 is a transcriptional coactivator for steroid receptors and nuclear receptors. It functions as a coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) []. Together with NCOA1, it is required to control energy balance between white and brown adipose tissues []. NCOA3 is overexpressed in a fraction of breast cancers and has been linked to prognosis and tamoxifen resistance [, ].
This conserved domain of unknown function is usually found tandemly repeated in the nuclear receptor coactivator family (NCOA1/2/3), also known as the SRC/p160 nuclear receptor coactivator family, which are ligand-dependent transcription factors [, ].NCOA1 directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion []. It is involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs) []. It is also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors [, , ]. It 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 []. It can be regulated by sumoylation and ubiquitination []. NCOA2 is a transcriptional coactivator for steroid receptors and nuclear receptors. It functions as a coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) []. Together with NCOA1, it is required to control energy balance between white and brown adipose tissues []. NCOA3 is overexpressed in a fraction of breast cancers and has been linked to prognosis and tamoxifen resistance [, ].
