NCOA1 (Nuclear receptor coactivator 1)
2018-02-01 Hasan Huseyin Kazan , Ufuk Gunduz AffiliationDepartment of Biological Sciences, Middle East Technical University, Ankara, Turkey, [email protected] (HHK); Department of Biological Sciences, Middle East Technical University, Ankara, Turkey [email protected] (UG)
Identity
HGNC
LOCATION
2p23.3 (Carapeti et al., 1998); Start: 24,492,050 bp; End: 24,770,702 bp; 278,652 bp; Orientation: Plus strand (GRCh38.p7)
IMAGE
LEGEND
Local order of NCOA1. Local order is shown together with leading and subsequent genes on chromosome 2. The direction of arrows indicates transcriptional directions on the chromosome and arrow sizes approximate gene sizes.
LOCUSID
ALIAS
F-SRC-1,KAT13A,RIP160,SRC1,bHLHe42,bHLHe74
FUSION GENES
Abstract
Review on NCOA1, with data on DNA, on the protein encoded, and where the gene is implicated.
DNA/RNA
Note
NCOA1 is the firstly cloned nuclear hormone receptor co-activator (Onate et al., 1995; Xu et al., 2009). The canonical transcript (ENST00000348332.7; NM_003743) includes 21 exons, 19 of which are encoded (GRCh38.p10; http://www.ensembl.org).
Numbers and illustrative sizes of exons of human NCOA1. Red boxes are the coding region and black boxes are the non-coding ones.
Transcription
Four alternatively spliced isoforms of NCOA1 have firstly been illustrated (Kamei et al., 1996). Compared to NCOA1a, NCOA1b lacks the N-termial domain, and NCOA1c, d and e have unique C-terminal sequences. NCOA1a and b have been shown to display diverse abilities to increase the estrogen receptor α ( ESR1 (Erα)) activity in cell lines (Kalkhoven et al., 1998; Xu et al., 2009). According to Ensembl database, there are eleven different transcripts of NCOA1 gene. Six of these transcripts encode two different proteins while five of them cannot encode protein. Lengths of the transcripts vary between 7405-501 bp (GRCh38.p10; http://www.ensembl.org).
Proteins
Note
NCOA1 gene encodes two similar proteins. The length of the canonical protein is 1441 amino acids with a molecular mass of 156,757 Da (UniPort ID: Q15788) and the length of the second protein is 1248 amino acids with a molecular mass of 135,621 Da (UniProt ID: B5MCN7). Like the other SRCs (NCOA2 and NCOA3 (SRC-2 and 3)), NCOA1 consists of three structural domains. The protein-protein interaction is performed via an N-terminal basic helix-loop-helix-Per/ARNT/Sim (bHLH-PAS) domain. This domain is highly conserved amongst p160 SRC family and promotes interaction with the transcription factors, such as myogenin, MEF-2C and TEF. The central domain which consists of LXXLL motifs forming amphipathic alpha-helices supports interaction with nuclear hormone receptors. The C-terminal domain includes two transcription activation domains, AD1 and AD2. AD1 binds and recruits CREBBP and EP300 (CBP and p300 histone acetyltransferase (HAT)) for chromatin remodeling, which is critical for SRC-mediated transcriptional activation. AD2 interacts with histone methyltransferases, coactivator-associated arginine methyltransferase 1 ( CARM1) and protein arginine methyltransferases ( PRMT1). The C-terminus of NCOA1, like SRC-3, also includes a HAT activity domain (Torchia et al., 1997; Xu et al., 2009).
Expression
Chen et al. showed that NCOA1 was expressed in placental labyrinth (Chen et al., 2010). According to The Human Protein Atlas database, NCOA1 is highly expressed in cerebral cortex, hippocampus, cerebellum, thyroid gland, parathyroid gland, adrenal gland, lymph node, nasopharynx, bronchus, gallbladder, pancreas, oral mucosa, esophagus, stomach, duodenum, small intestine, colon, rectum, kidney, urinary bladder, testis, fallopian tube, breast, vagina and placenta.
Expression profile of NCOA1 in human tissues. Data taken from The Human Protein Atlas (http://www.proteinatlas.org) in February, 2018.
Localisation
NCOA1 is synthesized in cytoplasm and imported into nucleus, and localized as speckles in both cytoplasm and nucleus. Localization to nucleus is performed thanks to nuclear localization signal located in between amino acids 18 and 36. After it display its function, it is exported to cytoplasm back, which is thought to inhibition of hormone action via NCOA1 degradation in cytoplasm. Exportation to cytoplasm back occurs owing to nuclear export signal located between amino acids 990 and 1038 (Amazit et al., 2003).
Structure and functions of NCOA1 protein. When hormone (H) is bound to nuclear hormone receptors (NR), they recruit NCOA1 and interact with it via LXXLL motif in NCOA1. NCOA1 interacts with CBP, p300, KAT2B (p/ CAF), CARM1 and PRMT1 and recruits these coactivators to the chromatin for chromatin remodeling. Remodeling of chromatin enables binding of transcription factors and RNA polymerase II on the promoter region. NR interacts with NCOA1 via not only NRID domain but bHLH/PAS domain, which is also important for function of NCOA1. Data adapted from Xu et al., 2009.
Function
NCOA1 increases the transcriptional activities of nuclear hormone receptors in a hormone-dependent manner. In addition to nuclear hormone receptors, NCOA1 and other SRCs are the coactivators of other transcription factors including NF-kB, Smads, E2F1, STATs, HIF1A, TP53, RB1, ETV4 (polyoma enhancer activator 3 (PEA3)) and ETS2. They support gene transcription by interacting with kinases, ubiquitin/sumoligases, phosphatases, histone acetyltransferases and histone methyltransferases (Qin et al., 2009; McBryan et al., 2012; Xu et al., 2009). Due to its role in transcription, NCOA1 and other SRCs have a role in different physiological functions, including cell cycle and energy metabolism. NCOA1 itself is critical for organ physiology. It has been showed that NCOA1 deficiency strongly influenced mice reproductive organ development (Xu et al., 1998). NCOA1-/- mice also displayed partial resistance to sex steroids and thyroid hormone (Weiss et al., 1999; Kamiya et al., 2003). NCOA1 is also important for the gluconeogenesis. In liver, it is a coactivator of CEBPA (CEBPα) which regulates the pyruvate carboxylase gene, the limiting enzyme for gluconeogenesis, together with PPARG (PPARγ). Activated PPARγ recruits NCOA1 and other coregulators, such as PGC-1 and CBP/p300 in brown fat, and deficiency in NCOA1 results in drawbacks in activity of PGC-1. This drawback further decreases energy expenditure and causes obesity with high fat diet (Xu et al., 2009).
Phosphorylation is critical in the functioning of SRC family proteins. Phosphorylation of SRCs alters their affinities for certain nuclear hormone receptors (Lopez et al., 2001; Rowan et al., 2000; Wu et al., 2004; Giamas et al., 2009). Moreover, phosphorylation by different kinases via different Ser/Thr amino acids results in determination of down-stream processes. NCOA1 could be phosphorylated by EGF, IL6, CAMP, CCNA2 (cyclin A2)/ CDK2, CDK1 and MAPK. Cyclin A2/Cdk2- and EGF-mediated phosphorylation increases progesterone receptor ( PGR)-dependent transcription while IL-6-induced phosphorylation supports androgen receptor ( AR)-dependent transcription via ligand independency. Additionally, cAMP-mediated phosphorylation of NCOA1 recruits p300 and CBP and activates PR-dependent transcription via ligand independency and MAPK-induced NCOA1 phosphorylation enhances the affinity of NCOA1 towards AR in prostate cancer cells (Rowan et al., 2000; Wu et al., 2004; Giamas et al., 2009; Ueda et al., 2002; Rowan et al., 2000b; Gregory et al., 2004; Xu et al., 2009; Moore and Weigel, 2011). In addition to phosphorylation, sumoylation of NCOA1 at Lys731 and Lys774 by SUMO1 was showed to increase the interaction between PR and NCOA1, and upregulate PR-mediated transcription (Chauchereau et al., 2003).
In hormone-dependent progesterone receptor activity, NCOA1 was shown to be down-regulated in hormone-dependent manner like PR to activate the transcription of target genes. NCOA1 down-regulation was illustrated to be predominantly in cytoplasmic compartment via proteasomal degradation and the down-regulation of NCOA1 together with PR is critical for the regulation of transcription (Amazit et al., 2011).
The interaction of NCOA1 with PR to regulate gene expression was partly underlined in a study where KAT7 (HBO1) (a member of the MYST acetylase family) was illustrated to modulate interaction of NCOA1 and PR in a hormone-dependent manner in human testis cell line, CV1 and human embryonic kidney cell line, HEK293 (Georgiakaki et al., 2006).
NCOA1 has been shown to affect developmental processes. NCOA1 and NCOA3 double knockout mice died at early embryonic stage while single knockout mice lived normally, pointing a cooperative role of NCOA1 and NCOA2 in embryo survival. Moreover, morphologies of labyrinths of NCOA1 (together with NCOA3) knockout mice embryos were abnormal via altered expression of genes responsible for placental morphogenesis, and glucose metabolism (Chen et al., 2010).
Baldwin et al. showed that high-risk human papillomavirus type 16 (HPV16) E7 oncoprotein affected the localization and function of NCOA1; relocalized NCOA1 into cytoplasm and decreased NCOA1-mediated gene expression and NCOA1-dependent histone acetyltransferase (HAT) activity in vivo and in vitro in cervical cancer cell line, HeLa (Baldwin et al., 2006).
NCOA1 has also been linked to glucose metabolism. Under glucose deprivation, NCOA1 was proved to stabilize 26S proteasome and affect the expression of complex I of the mitochondrial electron transport chain (Motamed et al., 2014).
Phosphorylation is critical in the functioning of SRC family proteins. Phosphorylation of SRCs alters their affinities for certain nuclear hormone receptors (Lopez et al., 2001; Rowan et al., 2000; Wu et al., 2004; Giamas et al., 2009). Moreover, phosphorylation by different kinases via different Ser/Thr amino acids results in determination of down-stream processes. NCOA1 could be phosphorylated by EGF, IL6, CAMP, CCNA2 (cyclin A2)/ CDK2, CDK1 and MAPK. Cyclin A2/Cdk2- and EGF-mediated phosphorylation increases progesterone receptor ( PGR)-dependent transcription while IL-6-induced phosphorylation supports androgen receptor ( AR)-dependent transcription via ligand independency. Additionally, cAMP-mediated phosphorylation of NCOA1 recruits p300 and CBP and activates PR-dependent transcription via ligand independency and MAPK-induced NCOA1 phosphorylation enhances the affinity of NCOA1 towards AR in prostate cancer cells (Rowan et al., 2000; Wu et al., 2004; Giamas et al., 2009; Ueda et al., 2002; Rowan et al., 2000b; Gregory et al., 2004; Xu et al., 2009; Moore and Weigel, 2011). In addition to phosphorylation, sumoylation of NCOA1 at Lys731 and Lys774 by SUMO1 was showed to increase the interaction between PR and NCOA1, and upregulate PR-mediated transcription (Chauchereau et al., 2003).
In hormone-dependent progesterone receptor activity, NCOA1 was shown to be down-regulated in hormone-dependent manner like PR to activate the transcription of target genes. NCOA1 down-regulation was illustrated to be predominantly in cytoplasmic compartment via proteasomal degradation and the down-regulation of NCOA1 together with PR is critical for the regulation of transcription (Amazit et al., 2011).
The interaction of NCOA1 with PR to regulate gene expression was partly underlined in a study where KAT7 (HBO1) (a member of the MYST acetylase family) was illustrated to modulate interaction of NCOA1 and PR in a hormone-dependent manner in human testis cell line, CV1 and human embryonic kidney cell line, HEK293 (Georgiakaki et al., 2006).
NCOA1 has been shown to affect developmental processes. NCOA1 and NCOA3 double knockout mice died at early embryonic stage while single knockout mice lived normally, pointing a cooperative role of NCOA1 and NCOA2 in embryo survival. Moreover, morphologies of labyrinths of NCOA1 (together with NCOA3) knockout mice embryos were abnormal via altered expression of genes responsible for placental morphogenesis, and glucose metabolism (Chen et al., 2010).
Baldwin et al. showed that high-risk human papillomavirus type 16 (HPV16) E7 oncoprotein affected the localization and function of NCOA1; relocalized NCOA1 into cytoplasm and decreased NCOA1-mediated gene expression and NCOA1-dependent histone acetyltransferase (HAT) activity in vivo and in vitro in cervical cancer cell line, HeLa (Baldwin et al., 2006).
NCOA1 has also been linked to glucose metabolism. Under glucose deprivation, NCOA1 was proved to stabilize 26S proteasome and affect the expression of complex I of the mitochondrial electron transport chain (Motamed et al., 2014).
Homology
NCOA2 (SRC-2, TIF2 or GRIP1) and NCOA3 (SRC-3, p/CIP, RAC3, AIB1, ACTR or TRAM-1) are homologous to NCOA1 and these three proteins are included in a family, called p160 SRC (Torchia et al., 1997; Xu et al., 2009).
Mutations
Note
A single nucleotide polymorphism (SNP) in NCOA1 (rs1804645; P1272S) was demonstrated to decrease ER activation while it increase protein life-time via blocking phosphorylation by glycogen synthase 3 ( GSK3B) in bone. Moreover, this SNP was linked to a decrease in hip and lumbar bone mineral density in women receiving tamoxifen (Hartmaier et al., 2011).
Another SNP in NCOA1 (rs7948087) was associated to multiple myeloma phenotype in Chinese Han population (Peng et al., 2017).
Four different SNPs in NCOA1 (rs11894248, rs17791703, rs7572475 and rs9309308) were linked to Kawasaki disease in Taiwanese people (Chen et al., 2014).
Two chromosomal rearrangements affecting NCOA1 in patients with sarcoma subtypes were identified. In one study, a novel t(2;2)(q35;p23) translocation generating PAX3/NCOA1 fusion protein has been shown (Wachtel et al., 2004). Similar fusion protein was proved to be a result of inv(2)(q35p23) mutation (Huang et al., 2016).
According to ClinVar database, huge chromosomal deletions and duplications in regions including NCOA1 gene have been submitted. These mutations showed to be pathogenic, benign or with uncertain significance.
Another SNP in NCOA1 (rs7948087) was associated to multiple myeloma phenotype in Chinese Han population (Peng et al., 2017).
Four different SNPs in NCOA1 (rs11894248, rs17791703, rs7572475 and rs9309308) were linked to Kawasaki disease in Taiwanese people (Chen et al., 2014).
Two chromosomal rearrangements affecting NCOA1 in patients with sarcoma subtypes were identified. In one study, a novel t(2;2)(q35;p23) translocation generating PAX3/NCOA1 fusion protein has been shown (Wachtel et al., 2004). Similar fusion protein was proved to be a result of inv(2)(q35p23) mutation (Huang et al., 2016).
According to ClinVar database, huge chromosomal deletions and duplications in regions including NCOA1 gene have been submitted. These mutations showed to be pathogenic, benign or with uncertain significance.
Implicated in
Top note
NCOA1 has widely been studied particularly in breast and prostate cancer through its interaction status with estrogen receptor alpha, progesterone receptor and androgen receptor.
Entity name
Breast Cancer
Note
NCOA1 has been shown to be generally over-expressed in breast cancer. Moreover, its over-expression has been correlated with ERBB2 expression, metastasis, cancer recurrence and poor disease-free survival (Wang et al., 2006; Fleming et al., 2004; Myers et al., 2004; Hudelist et al., 2003; McBryan et al., 2012; Qin et al., 2014; 2015). Furthermore, NCOA1 has also been demonstrated to be a predictor of breast cancer recurrence after therapy (Redmond et al., 2009). In a cohort study, NCOA1 was found to be over-expressed in 155 of 312 breast cancer patients underwent radical resection, and NCOA1 expression was demonstrated to be correlated with Ki-67 and HER-2 expression. Moreover, NCOA1 and NANOG coexpression was showed to be significantly poorer postoperative disease-specific survival than those with no expression in the HER-2-positive group (Jin et al., 2016). In a study, NCOA1 expression has also been correlated with a favorable response to tamoxifen in patients with recurrent breast cancer (Berns et al., 1998). However, it has been showed that protein kinase A (PKA)-mediated of phosphorylation of estrogen receptor alpha at S305 caused alteration in orientation between ERα and NCOA1 leading to active transcription complex even in the presence of tamoxifen, resulting tamoxifen resistance in T47D and MCF7 breast cancer cell lines (Zwart et al., 2007). Not only tamoxifen response, NCOA1 was shown to be involved in resistance to aromatase inhibitors in patient with breast cancer and breast cancer cell model. NCOA1 was proved to be over-expressed in aromatase-resistant cells and patient tumors. NCOA1 was demonstrated to interact with transcription factor Ets2 and regulate transcription of MYC and MMP9 by which it affected tumor aggressiveness (McBryan et al., 2012). In breast adenocarcinoma cell line, MCF7, NCOA1 has been illustrated to have a role in ERα-mediated cell growth (Tai et al., 2000; Cavarretta et al., 2002). What is more, NCOA1 was shown to co-operate with MUC1, an ERα interactive protein (Wei et al., 2006). NCOA1 has been also involved in cell proliferation and invasion via autocrine/paracrine activity of the SDF-1α- CXCL12 signaling pathway in MCF7 cell lines (Kishimoto et al., 2005). In another study, NCOA1 has been proved to support epithelial-mesenchymal transition (EMT), invasion, migration and metastasis of breast tumor cells via activating PEA3-mediated Twist ( TWIST1) expression (Qin et al., 2009; Xu et al., 2009). In human ductal breast epithelial cell line, T47D, cyclin A2/Cdk2 was proved to phosphorylate NCOA1 and thus increase NCOA1/PR interaction and PR activity. Cyclin A2/Cdk2 as well as Cdk1 was further showed to phosphorylate seventeen sites in NCOA1 protein (Moore and Weigel, 2011). In vivo animal model studies have also proved the function of NCOA1 in breast tumorigenesis. Importantly, in vivo NCOA1 knockdown was showed to cause reduction in expression of ERBB2, activation of Akt, inhibition of colony stimulating factor 1 ( CSF1) and prevention of macrophage recruitment to the tumor environment (Wang et al., 2009). Metastasis-focused study in mice figured out that NCOA1, together with FOS, up-regulated macrophage attractant CSF1 and increased macrophage recruitment, and metastasis (Qin et al., 2014). In a study conducted by Qin et al. NCOA1 was determined to up-regulate VEGFA by associating with FOS and HIF1α, potentiating angiogenesis in breast cancer mice models (Qin et al., 2015). Wang et al. proposed cardiac glycoside bufalin as an inhibitor of both SRC-3 and NCOA1, and showed that bufalin treatment decreased tumor growth in a mouse xenograft model of breast cancer (Wang et al., 2014).
Entity name
Prostate Cancer
Note
The expression profile of NCOA1 was not high in human tumors in general (Maki et al., 2006). Still, some studies proposed the expression of NCOA1 was correlated with tumor grade (Agoulnik et al., 2005; Gregory et al., 2001; Fujimoto et al., 2001). In one study, NCOA1 was shown to be more located to nucleus in androgen-independent prostate tumors (Maki et al., 2006). NCOA1 was demonstrated to increase AR-dependent cell proliferation in prostate cancer cell lines. Thus, NCOA1 knockdown was parallel to inhibition of proliferation in androgen-dependent prostate cancer cell lines, LNCaP and C4-2 while it did not affect the proliferation of AR-negative prostate cancer cell lines, PC-3 and DU145 (Agoulnik et al., 2005). This effect was further characterized by Luef et al. and proved that the effect was a result of upregulation of protein kinase D1 ( PRKD1) which was negatively regulated by AR. They also showed that the expression of NCOA1 was high in patients with prostate cancer (Luef et al., 2016). Overall, NCOA1 supports prostate carcinogenesis in an androgen-dependent and -independent manner (Xu et al., 2009). However, in vivo murine studies have showed that NCOA1 did not affect the prostate cancer tumorigenesis while other SRC family member, SRC-3 was critically affected (Tien et al., 2006).
Entity name
Endometrial Cancer
Note
NCOA1 phosporylation was demonstrated to significantly enhance agonistic activity of tamoxifen in endometrial cancer, pointing a possible function of NCOA1 in tamoxifen-induced proliferation and enhancement in risk of endometrial cancer via tamoxifen therapy (Shang and Brown, 2002; Shah and Rowan, 2005).
Entity name
Hepatoma
Note
NCOA1 together with PPARGC1A (PGC1α) was proved to be down-regulated in hepatoma cell line, HepG2 where it critically coactivates hepatocyte nuclear factor 4α ( HNF4A) which is fundamental for liver development and hepatic gene expression. Overexpression of both NCOA1 and PCG1α increase the expression of HNF4α-regulated genes and triggered differentiation of HepG2 cells (Martinez-Himenez et al., 2006). Ma et al. showed thatMIR105-1 targeted NCOA1 in hepatocellular carcinoma. They checked the expression levels of miR-105-1 and demonstrated that it was down-regulated in samples from patients with hepatocellular carcinoma compared to those of normal individuals. Moreover, down-regulation of miR-105-1 and up-regulation of NCOA1, as a result, were correlated with shorter overall survival (OS) and progression free survival (PFS) in hepatocellular carcinoma (Ma et al., 2017).
Entity name
Colon cancer
Note
In colorectal cancer-derived cell lines, DLD-1, HT29 and HCT116, leptin and insulin signaling, via ERK1/2, were showed to increase MIR4443 targeting and down-regulating both TRAF4 and NCOA1. Down-regulation of TRAF4 and NCOA1 was illustrated to suppress invasion and proliferation of these cell lines (Meerson and Yehuda, 2016).
Entity name
Cervical cancer
Note
In cervical cancer cell line, HeLa overexpressing HPV16 E7, this epitope has been shown to relocalize NCOA1 into cytoplasm and decrease NCOA1-dependent transcription via disrupting association with HAT (Baldwin et al., 2006).
Entity name
Note
In a cohort study with multiple myeloma patients in China, single nucleotide polymorphism in NCOA1 gene (rs7948087) was shown to strongly associate with multiple myeloma phenotype, pointing NCOA1 as a susceptibility gene for multiple myeloma patients in Chinese Han population (Peng et al., 2017).
Entity name
Head and neck squamous cell carcinoma
Note
In a clinical study, Pavon et al. showed that expression of NCOA1 and creatine kinase mitochondrial 1(CKMT1) had prognostic significance in advanced-stage head and neck carcinoma (Pavon et al., 2015).
Entity name
Sarcoma
Note
Rhabdomyosarcoma is a soft sarcoma and is able to subclassified in to two groups: embryonal rhabdomyosarcoma ID: 5193> and alveolar rhabdomyosarcoma. In a microarray-based study, a novel translocation t(2;2)(q35;p23) causing a fusion PAX3/NCOA1 protein (Wachtel et al., 2004). In another study, in biphenotypic sinonasal sarcoma cases where t(2;4)(q36;q31) PAX3/ MAML3 fusion has already been known, novel PAX3/NCOA1 fusion has been demonstrated via inv(2)(q35p23). These cases were underlined to display desmin reactivity and a small component of rhabdomyoblastic cells (Huang et al., 2016).
Entity name
Endometriosis
Note
Endometriosis (EMS; ectopic endometrium) is an estrogen-dependent and inflammatory complex disease where immunological factors and angiogenesis play a pivotal role in its pathogenesis (Gazvani and Templeton, 2006; Rizner 2009). Shi et al. showed that the expression of NCOA1 was greater in ectopic endometrium than that of normal endometrium, and NCOA1 was involved in the expression of stromal cell-derived factor 1 (SCDF1/CXCL12) whose expression was induced by estradiol (Shi et al., 2014).
Entity name
Obesity
Note
NCOA1 together with p/CIP was demonstrated to control insulin signaling in vitro and in vivo. Knockout of these genes resulted in increase in glucose uptake and insulin sensitivity in both regular chow- and high fat diet-fed mice. Moreover, knockouts also brought about resistance to age-related obesity and glucose intolerance through increase in the levels of insulin receptor substrate 1 ( IRS1; Wang et al., 2012).
Entity name
Inflammation
Note
Isoflavone biochanin A treatment of thymoma cell line, EL4 increased the levels ofIL7 which was linked to autoimmunity, chronic inflammation and protection against infections. This function of Biochanin A was proved to be a result of enhanced interaction between retinoic acid receptor-related orphan receptor RORC and NCOA1 via phosphorylation of signal transducer and activator of transcription 3 (STAT3; Takahashi et al., 2017).
Entity name
Kawasaki disease
Note
Kawasaki disease is a self-limited, acute and systemic vasculitis. Chen et al. showed that four SNPs (rs11894248, rs17791703, rs7572475 and rs9309308) in NCOA1 were associated with Kawasaki disease in 327 Taiwanese people (Chen et al., 2014).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16140968 | 2005 | Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression. | Agoulnik IU et al |
| 12791702 | 2003 | Subcellular localization and mechanisms of nucleocytoplasmic trafficking of steroid receptor coactivator-1. | Amazit L et al |
| 21273440 | 2011 | Ligand-dependent degradation of SRC-1 is pivotal for progesterone receptor transcriptional activity. | Amazit L et al |
| 16775354 | 2006 | Human papillomavirus E7 oncoprotein dysregulates steroid receptor coactivator 1 localization and function. | Baldwin A et al |
| 9541193 | 1998 | Predictive value of SRC-1 for tamoxifen response of recurrent breast cancer. | Berns EM et al |
| 9782096 | 1998 | Assignment of the steroid receptor coactivator-1 (SRC-1) gene to human chromosome band 2p23. | Carapeti M et al |
| 11818499 | 2002 | Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation. | Cavarretta IT et al |
| 12529333 | 2003 | Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC-1. | Chauchereau A et al |
| 20685850 | 2010 | The cooperative function of nuclear receptor coactivator 1 (NCOA1) and NCOA3 in placental development and embryo survival. | Chen X et al |
| 24652666 | 2014 | Association between SRC-1 gene polymorphisms and coronary artery aneurysms formation in Taiwanese children with Kawasaki disease. | Chen YT et al |
| 15452162 | 2004 | Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1. | Fleming FJ et al |
| 11489729 | 2001 | Different expression of androgen receptor coactivators in human prostate. | Fujimoto N et al |
| 11866688 | 2002 | Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. | Gazvani R et al |
| 16645042 | 2006 | Ligand-controlled interaction of histone acetyltransferase binding to ORC-1 (HBO1) with the N-terminal transactivating domain of progesterone receptor induces steroid receptor coactivator 1-dependent coactivation of transcription. | Georgiakaki M et al |
| 19339517 | 2009 | CK1delta modulates the transcriptional activity of ERalpha via AIB1 in an estrogen-dependent manner and regulates ERalpha-AIB1 interactions. | Giamas G et al |
| 14662770 | 2004 | Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer. | Gregory CW et al |
| 22174377 | 2012 | A SNP in steroid receptor coactivator-1 disrupts a GSK3β phosphorylation site and is associated with altered tamoxifen response in bone. | Hartmaier RJ et al |
| 26371783 | 2016 | Novel PAX3-NCOA1 Fusions in Biphenotypic Sinonasal Sarcoma With Focal Rhabdomyoblastic Differentiation. | Huang SC et al |
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| 15917309 | 2005 | The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1alpha/CXCL12. | Kishimoto H et al |
| 11301320 | 2001 | Growth factors signal to steroid receptors through mitogen-activated protein kinase regulation of p160 coactivator activity. | Lopez GN et al |
| 27255895 | 2016 | The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1. | Luef B et al |
| 16894533 | 2006 | Screening of genetic and expression alterations of SRC1 gene in prostate cancer. | Mäki HE et al |
| 28060733 | 2017 | High expression of miR-105-1 positively correlates with clinical prognosis of hepatocellular carcinoma by targeting oncogene NCOA1. | Ma YS et al |
| 16891307 | 2006 | Underexpressed coactivators PGC1alpha and SRC1 impair hepatocyte nuclear factor 4 alpha function and promote dedifferentiation in human hepatoma cells. | Martínez-Jiménez CP et al |
| 22108824 | 2012 | Metastatic progression with resistance to aromatase inhibitors is driven by the steroid receptor coactivator SRC-1. | McBryan J et al |
| 27842582 | 2016 | Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells. | Meerson A et al |
| 21550420 | 2011 | Regulation of progesterone receptor activity by cyclin dependent kinases 1 and 2 occurs in part by phosphorylation of the SRC-1 carboxyl-terminus. | Moore NL et al |
| 24438340 | 2014 | Steroid receptor coactivator 1 is an integrator of glucose and NAD+/NADH homeostasis. | Motamed M et al |
| 15477868 | 2004 | Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine-resistant breast cancer. | Myers E et al |
| 7481822 | 1995 | Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. | Oñate SA et al |
| 26516695 | 2016 | CKMT1 and NCOA1 expression as a predictor of clinical outcome in patients with advanced-stage head and neck squamous cell carcinoma. | Pavón MA et al |
| 28264017 | 2017 | NCOA1 is a novel susceptibility gene for multiple myeloma in the Chinese population: A case-control study. | Peng M et al |
| 19383905 | 2009 | The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. | Qin L et al |
| 24769444 | 2014 | NCOA1 Directly Targets M-CSF1 Expression to Promote Breast Cancer Metastasis. | Qin L et al |
| 26287601 | 2015 | NCOA1 promotes angiogenesis in breast tumors by simultaneously enhancing both HIF1α- and AP-1-mediated VEGFa transcription. | Qin L et al |
| 19276281 | 2009 | Coassociation of estrogen receptor and p160 proteins predicts resistance to endocrine treatment; SRC-1 is an independent predictor of breast cancer recurrence. | Redmond AM et al |
| 19524121 | 2009 | Estrogen metabolism and action in endometriosis. | Rizner TL et al |
| 11073973 | 2000 | 8-Bromo-cyclic AMP induces phosphorylation of two sites in SRC-1 that facilitate ligand-independent activation of the chicken progesterone receptor and are critical for functional cooperation between SRC-1 and CREB binding protein. | Rowan BG et al |
| 10660621 | 2000 | Phosphorylation of steroid receptor coactivator-1. Identification of the phosphorylation sites and phosphorylation through the mitogen-activated protein kinase pathway. | Rowan BG et al |
| 15528270 | 2005 | The Src kinase pathway promotes tamoxifen agonist action in Ishikawa endometrial cells through phosphorylation-dependent stabilization of estrogen receptor (alpha) promoter interaction and elevated steroid receptor coactivator 1 activity. | Shah YM et al |
| 11923541 | 2002 | Molecular determinants for the tissue specificity of SERMs. | Shang Y et al |
| 10623616 | 2000 | Involvement of nuclear receptor coactivator SRC-1 in estrogen-dependent cell growth of MCF-7 cells. | Tai H et al |
| 28579428 | 2017 | Biochanin A enhances RORγ activity through STAT3-mediated recruitment of NCOA1. | Takahashi M et al |
| 19305643 | 2009 | The role of SRC-1 in murine prostate cancinogenesis is nonessential due to a possible compensation of SRC-3/AIB1 overexpression. | Tien JC et al |
| 9192892 | 1997 | The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. | Torchia J et al |
| 12163482 | 2002 | Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells. | Ueda T et al |
| 15313887 | 2004 | Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1. | Wachtel M et al |
| 19109434 | 2009 | Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation. | Wang S et al |
| 24390736 | 2014 | Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1. | Wang Y et al |
| 22859932 | 2012 | The transcriptional coactivators p/CIP and SRC-1 control insulin resistance through IRS1 in obesity models. | Wang Z et al |
| 16427018 | 2006 | MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. | Wei X et al |
| 10202153 | 1999 | Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. | Weiss RE et al |
| 15383283 | 2004 | Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling pathways. | Wu RC et al |
| 9506940 | 1998 | Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. | Xu J et al |
| 19701241 | 2009 | Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. | Xu J et al |
| 17627277 | 2007 | PKA-induced resistance to tamoxifen is associated with an altered orientation of ERalpha towards co-activator SRC-1. | Zwart W et al |
Other Information
Locus ID:
NCBI: 8648
MIM: 602691
HGNC: 7668
Ensembl: ENSG00000084676
Variants:
dbSNP: 8648
ClinVar: 8648
TCGA: ENSG00000084676
COSMIC: NCOA1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA443560 | Breast Neoplasms | Disease | ClinicalAnnotation | associated | PD | 22174377 | |
| PA451581 | tamoxifen | Chemical | ClinicalAnnotation | associated | PD | 22174377 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38506084 | 2024 | Steroid receptor coactivator 1 promotes human hepatocellular carcinoma invasiveness through enhancing MMP-9. | 1 |
| 38506084 | 2024 | Steroid receptor coactivator 1 promotes human hepatocellular carcinoma invasiveness through enhancing MMP-9. | 1 |
| 37402091 | 2023 | Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma. | 0 |
| 37402091 | 2023 | Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma. | 0 |
| 35137184 | 2022 | Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities. | 4 |
| 35418691 | 2022 | Nuclear receptor coactivator SRC-1 promotes colorectal cancer progression through enhancing GLI2-mediated Hedgehog signaling. | 4 |
| 35137184 | 2022 | Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities. | 4 |
| 35418691 | 2022 | Nuclear receptor coactivator SRC-1 promotes colorectal cancer progression through enhancing GLI2-mediated Hedgehog signaling. | 4 |
| 33090636 | 2021 | Steroid receptor coactivator-1 enhances the stemness of glioblastoma by activating long noncoding RNA XIST/miR-152/KLF4 pathway. | 13 |
| 33574497 | 2021 | Recurrent MEIS1-NCOA2/1 fusions in a subset of low-grade spindle cell sarcomas frequently involving the genitourinary and gynecologic tracts. | 8 |
| 33576087 | 2021 | Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma. | 10 |
| 34272753 | 2021 | PRRX1-NCOA1-rearranged fibroblastic tumour: a clinicopathological, immunohistochemical and molecular genetic study of six cases of a potentially under-recognised, distinctive mesenchymal tumour. | 1 |
| 33090636 | 2021 | Steroid receptor coactivator-1 enhances the stemness of glioblastoma by activating long noncoding RNA XIST/miR-152/KLF4 pathway. | 13 |
| 33574497 | 2021 | Recurrent MEIS1-NCOA2/1 fusions in a subset of low-grade spindle cell sarcomas frequently involving the genitourinary and gynecologic tracts. | 8 |
| 33576087 | 2021 | Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma. | 10 |
Citation
Hasan Huseyin Kazan ; Ufuk Gunduz
NCOA1 (Nuclear receptor coactivator 1)
Atlas Genet Cytogenet Oncol Haematol. 2018-02-01
Online version: http://atlasgeneticsoncology.org/gene/44097/teaching-explorer/gene-fusions/deep-insight-explorer/meetings/
