Affinage

NCOA3

Nuclear receptor coactivator 3 · UniProt Q9Y6Q9

Length
1424 aa
Mass
155.3 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCOA3 (AIB1/SRC-3/ACTR/p/CIP/TRAM-1) is a multifunctional transcriptional coactivator that couples ligand-activated nuclear receptors to chromatin-modifying machinery to drive hormone-dependent gene expression, growth, and oncogenesis (PMID:9252329, PMID:9267036). It binds nuclear receptors including estrogen receptor, thyroid hormone receptor, androgen receptor, and ERRα in a ligand-dependent manner through LXXLL/helical interaction motifs, with crystallographic and binding data defining receptor selectivity (PMID:9252329, PMID:9346901, PMID:10965917, PMID:20086010, PMID:19491275). Bound to receptors and to non-receptor factors such as E2F1, NF-κB, AP-1, PEA3, and STAT6, NCOA3 functions as an intrinsic histone acetyltransferase and as an assembly platform that recruits CBP/p300, P/CAF, and GCN5 acetyltransferases and the arginine methyltransferase CARM1 to target promoters (PMID:9267036, PMID:12885766, PMID:15169882, PMID:15145939, PMID:18593949); its activation domain is intrinsically disordered and folds upon binding the NCBD of CBP/p300 (PMID:18177052). NCOA3 activity and abundance are governed by an extensive post-translational network: activating phosphorylation by MAPK, IKK, c-Abl, CK1δ, and p38MAPK (PMID:10866661, PMID:11971985, PMID:16456540, PMID:18765637, PMID:19339517); cell-cycle phosphorylation by CDK1/Cyclin B that excludes it from mitotic chromatin (PMID:22163316); counteracting dephosphorylation and stabilization by PP1/PP2A/PDXP (PMID:18922467); sumoylation by PIAS1 and arginine methylation by CARM1 that restrain activity (PMID:17043108, PMID:22283414); and proteasomal degradation through the REGγ/20S proteasome and the PTEN–Fbw7α ubiquitin pathway (PMID:16439211, PMID:23514585). Its subcellular distribution is set by microtubule-dependent nuclear–cytoplasmic shuttling, with histone acetyltransferase activity confined to nuclear complexes (PMID:12192059). In vivo, NCOA3 is required for normal growth, female reproduction, and mammary development (PMID:10823921), for embryonic stem cell pluripotency via Esrrb and Nanog (PMID:23019124, PMID:22977234), and for regulatory T cell induction (PMID:33564037), while its oncogenic overexpression drives breast and prostate cancer through an autocrine IGF-I/PI3K/AKT loop, MMP-mediated invasion, and EMT (PMID:15380517, PMID:14996752, PMID:18644862, PMID:23762395).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 High

    Established NCOA3 as a ligand-dependent nuclear receptor coactivator with intrinsic enzymatic activity, defining its core molecular function.

    Evidence Co-IP, reporter assays, in vitro HAT assays, and far-Western cloning across ER, TR, and other nuclear receptors

    PMID:9192892 PMID:9252329 PMID:9267036 PMID:9346901

    Open questions at the time
    • In vivo target gene repertoire not yet mapped
    • Distinct binding surfaces among coactivators only partially resolved
  2. 2000 High

    Linked growth-factor signaling to coactivator output and demonstrated physiological in vivo requirement, showing NCOA3 integrates kinase signaling with hormone action.

    Evidence In vitro/in vivo MAPK kinase assays, endogenous co-IP in MCF-7 cells, and a SRC-3 knockout mouse with growth and reproductive phenotypes; AR coactivation by yeast two-hybrid and reporter assays

    PMID:10823921 PMID:10866661 PMID:10965917 PMID:11050174

    Open questions at the time
    • Specific MAPK phosphosites mapped only later
    • Tissue-specific contributions to knockout phenotype unresolved
  3. 2002 High

    Defined NCOA3 regulation of NF-κB signaling and the spatial control of its activity, showing compartment dictates enzymatic function.

    Evidence Biochemical purification with MS, IKK kinase assay, TNFα-induced translocation; immunofluorescence, GFP imaging, leptomycin B, and HAT assays mapping CRM1-dependent shuttling

    PMID:11971985 PMID:12192059

    Open questions at the time
    • Trigger linking cell-cycle phase to shuttling not defined
    • How cytoplasmic pool is reactivated unresolved
  4. 2004 High

    Identified the oncogenic mechanism of NCOA3 overexpression in cancer and a receptor-independent proliferative route via E2F1.

    Evidence Transgenic and knockout mouse tumor models, RNAi, ChIP at E2F and IGF-I loci, PI3K/AKT pathway analysis, and ERα degradation assays

    PMID:14996752 PMID:15169882 PMID:15289619 PMID:15380517

    Open questions at the time
    • Relative contribution of receptor-dependent vs E2F1 routes in tumors unquantified
    • Direct vs indirect IGF-I transcriptional control not fully resolved
  5. 2006 High

    Resolved how NCOA3 abundance and activity are turned down through proteolysis and modification, establishing a layered degradation/PTM control system.

    Evidence In vitro reconstitution with purified REGγ/20S proteasome, in vivo sumoylation/phosphorylation assays, p38MAPK kinase assays in RARα context, and CARM1 in vitro methylation with KO MEF validation

    PMID:16439211 PMID:16456540 PMID:16760465 PMID:17043108

    Open questions at the time
    • Interplay/ordering of competing modifications not integrated
    • Cellular cues selecting degradation route unclear
  6. 2008 High

    Expanded the kinase and phosphatase regulatory map and structurally explained coactivator folding and AR selectivity, plus invasion/metastasis functions.

    Evidence c-Abl kinase assays with phospho-mutants, phosphatase functional genomic screen with in vitro dephosphorylation, NMR of the ACTR–CBP complex, ChIP at MMP promoters, and knockout PyMT metastasis models

    PMID:18177052 PMID:18593949 PMID:18644862 PMID:18765637 PMID:18922467

    Open questions at the time
    • Combinatorial logic of multiple phosphosites unresolved
    • Phosphatase substrate specificity in vivo incompletely defined
  7. 2010 High

    Provided structural basis for AR-coactivator preference and extended coactivation to ERRα and neuronal miRNA pathways.

    Evidence Crystal structure of SRC3-AR with patient mutation analysis, ATBF1 competition assays, FRET/two-hybrid/endogenous co-IP for ERRα, and Ncoa3 knockdown affecting Ago2 and dendritic morphology

    PMID:19491275 PMID:20086010 PMID:20720010 PMID:26105073

    Open questions at the time
    • Generality of LXXLL synergy across receptors untested
    • Mechanism of Ago2 transcriptional control not defined
  8. 2012 High

    Established NCOA3 roles in stem cell pluripotency, mitotic chromatin exclusion, and metabolic regulation, broadening its physiological scope.

    Evidence Co-IP and ChIP-seq with Esrrb in ESCs, ChIP at Nanog promoter, CDK1/Cyclin B kinase assays with mitotic fractionation, PIAS1 E3-mutant sumoylation assays, and double-knockout metabolic mouse models

    PMID:22163316 PMID:22283414 PMID:22859932 PMID:22977234 PMID:23019124

    Open questions at the time
    • Direct vs indirect pluripotency targets partially resolved
    • Functional consequence of mitotic redistribution on later transcription unclear
  9. 2014 Medium

    Connected NCOA3 to ubiquitin-bridge degradation, chromatin remodeling at mucin loci, EMT, and UPR signaling, linking it to cancer cell plasticity and stress responses.

    Evidence PTEN-Fbw7α bridging co-IP/ubiquitination assays, SNAI1 promoter and E-cadherin analyses, MUC4 nuclease accessibility/FUT8 assays, and XBP1-PERK-ATF4 UPR feedback experiments

    PMID:23514585 PMID:23762395 PMID:25531332 PMID:27109102

    Open questions at the time
    • Most mechanisms from single labs without reciprocal validation
    • Direct vs cofactor-mediated chromatin remodeling at MUC4 not separated
  10. 2018 Medium

    Identified additional degradation regulators and a cancer stem cell function, supporting NCOA3 as a therapeutic target.

    Evidence MAD2L2/p38-dependent ubiquitination assays and tumor models; PELP1-AIB1 complex with Thr24 phospho-readout, SI-2 inhibition, and tumorsphere assays

    PMID:29348189 PMID:29360267

    Open questions at the time
    • Single-lab mechanisms awaiting independent confirmation
    • Direct kinase responsible for Thr24 phosphorylation not defined
  11. 2021 Medium

    Extended NCOA3 function to immune regulation, showing a requirement for regulatory T cell induction and suppressive activity.

    Evidence Bioinformatic enrichment plus cellular loss-of-function and pharmacological inhibition with T cell suppression assays

    PMID:33564037

    Open questions at the time
    • Transcriptional targets in Tregs not identified
    • Mechanism of SRC-3 enrichment in Tregs unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozens of competing post-translational modifications, degradation routes, and partner interactions are dynamically integrated to set NCOA3 activity in a given cellular and disease context remains unresolved.
  • No unified quantitative model of PTM crosstalk
  • Context-specific target gene programs not systematically mapped
  • Structural basis of full-length complex assembly unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3
Partners
ARCARM1E2F1EP300ESR1ESRRAESRRBPELP1
Complex memberships
CBP/p300 coactivator complexIKK complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 AIB1 (NCOA3) protein interacts with estrogen receptors in a ligand-dependent fashion and enhances estrogen-dependent transcription when transfected into cells. Co-immunoprecipitation, transfection/reporter assay Science High 9252329
1997 ACTR (NCOA3) is a histone acetyltransferase that directly binds nuclear receptors in a hormone-dependent manner and recruits CBP and P/CAF to form a multisubunit coactivator complex containing at least three classes of histone acetyltransferases. In vitro HAT assay with purified ACTR, co-immunoprecipitation, direct binding assay Cell High 9267036
1997 p/CIP (NCOA3) is present in cells as a complex with CBP and is required for transcriptional activity of nuclear receptors and CBP/p300-dependent transcription factors; leucine-rich charged helical interaction motifs in p/CIP are required for receptor-specific gene activation. Co-immunoprecipitation, transfection/reporter assay, deletion mutagenesis Nature High 9192892
1997 TRAM-1 (NCOA3) binds thyroid hormone receptor and other nuclear receptors in a ligand-dependent manner via a region outside the AF-2 domain (including helix 3 of the ligand binding domain), distinct from SRC-1 binding. Far-Western expression screening, GST pulldown, transfection/reporter assay, AF-2 and helix-3 mutant TR binding assays The Journal of biological chemistry High 9346901
2000 AIB1 (NCOA3) is a phosphoprotein that is phosphorylated in vitro and in vivo by MAPK; MAPK phosphorylation of AIB1 enhances its transcriptional activity and stimulates recruitment of p300 and associated histone acetyltransferase activity, providing a mechanism for growth factor modulation of estrogen action. In vitro kinase assay, in vivo phosphorylation analysis, co-immunoprecipitation, reporter assay Molecular and cellular biology High 10866661
2000 Endogenous AIB1 and estrogen receptor form a ligand-specific complex in MCF-7 breast cancer cells detectable by immunoprecipitation; complex formation is observed with estradiol but much less with the partial agonist monohydroxytamoxifen. In vitro binding affinity of mouse ER for AIB1 is ~40–120 nM. Immunoprecipitation of endogenous proteins, in vitro binding assay Proceedings of the National Academy of Sciences of the United States of America High 11050174
2000 SRC-3/NCOA3 knockout mice exhibit dwarfism, delayed puberty, reduced female reproductive function, and blunted mammary gland development, demonstrating in vivo roles in the growth hormone regulatory pathway and estrogen production. Genetic knockout mouse model with hormonal and phenotypic analysis Proceedings of the National Academy of Sciences of the United States of America High 10823921
2000 TRAM-1 (NCOA3) acts as an androgen receptor (AR) coactivator: it binds the AR ligand-binding domain and the N-terminal/DNA-binding domains in a ligand-dependent manner and enhances DHT-dependent AR transactivation ~5-fold in cell-based assays. Yeast two-hybrid, GST affinity matrix binding assay, transfection/reporter assay, immunohistochemistry Endocrinology Medium 10965917
2002 SRC-3 (NCOA3) associates with the IκB kinase (IKK) complex (but not SRC-1), is phosphorylated by IKK in vitro, and undergoes TNFα-induced phosphorylation and translocation from cytoplasm to nucleus in cells; SRC-3 enhances NF-κB-mediated gene expression in concert with IKK. Biochemical purification of SRC-3 protein complexes, mass spectrometry identification, in vitro kinase assay, subcellular fractionation/immunofluorescence, reporter assay, SRC-3 null mouse gene expression analysis Molecular and cellular biology High 11971985
2002 p/CIP (NCOA3) is predominantly cytoplasmic in many cell types; nuclear import and export are regulated by an N-terminal nuclear import signal and C-terminal leucine-rich CRM1-dependent nuclear export sequences; cytoplasmic shuttling is cell cycle-dependent (S and late M phases) and requires an intact microtubule network; only nuclear p/CIP complexes possess histone acetyltransferase activity. Immunofluorescence, live cell imaging with GFP fusions, leptomycin B treatment, immunoaffinity purification with HAT assay, deletion/point mutagenesis, fractionation Molecular and cellular biology High 12192059
2003 p/CIP (NCOA3) recruits GCN5 histone acetyltransferase via its AD1 activation domain to facilitate RARα-dependent transcription; two helical motifs within AD1 are required for interactions with both GCN5 and CBP. Yeast genetic screen (SAGA component mutants), co-immunoprecipitation, siRNA knockdown, reporter assay, deletion and point mutagenesis The Journal of biological chemistry High 12885766
2004 ACTR/NCOA3 directly interacts with E2F1 through its N-terminal domain and is recruited to E2F target gene promoters, stimulating transcription of G1/S transition genes independently of estrogen receptor, thereby promoting breast cancer cell proliferation and antiestrogen resistance. Co-immunoprecipitation, chromatin immunoprecipitation, adenoviral RNAi, reporter assay, cell proliferation assay Molecular and cellular biology High 15169882
2004 AIB1 coactivator uniquely mediates agonist-induced (but not antagonist-induced) ERα degradation via the ubiquitin-proteasome machinery; AIB1 recruitment by ERα is both necessary and sufficient to promote ERα degradation and is required for RNA polymerase II recruitment to ERα target promoters. RNAi knockdown, chromatin immunoprecipitation, reporter assay, Western blot for ERα stability Proceedings of the National Academy of Sciences of the United States of America High 15289619
2004 AIB1 overexpression in transgenic mice leads to increased mammary IGF-I mRNA and serum IGF-I protein, with activation of IGF-I receptor and downstream PI3K/AKT signaling in mammary epithelial cells; AIB1 knockdown in tumor cells reduces IGF-I mRNA and increases apoptosis, demonstrating an autocrine IGF-I loop as the oncogenic mechanism. Transgenic mouse model, siRNA knockdown, signaling pathway analysis (Western blot for IGF-IR, PI3K/AKT), apoptosis assay Cancer cell High 15380517
2004 AIB1 deficiency in AIB1(-/-)/v-Ha-ras mice causes partial resistance to IGF-I signaling due to significant reduction in insulin receptor substrates, suppressing mammary tumorigenesis and metastasis by inhibiting cell proliferation and migration. Genetic knockout in mammary tumor model, IGF-I signaling pathway analysis, tumor incidence assay Cancer research High 14996752
2004 p/CIP (NCOA3) acts as a positive regulator of STAT6 transcriptional activation by indirectly interacting with STAT6 via p300/CBP; overexpression of the CBP-interacting domain of p/CIP blocks STAT6-mediated transactivation and CD23 expression in IL-4-stimulated B cells. ChIP demonstrates IL-4-induced recruitment of p/CIP to the IgH germ-line ε promoter. Co-immunoprecipitation, reporter assay, chromatin immunoprecipitation, overexpression/dominant-negative approach The Journal of biological chemistry Medium 15145939
2006 SRC-3/AIB1 (NCOA3) is degraded by the REGγ proteasome in a ubiquitin- and ATP-independent manner; REGγ directly interacts with SRC-3 and promotes its degradation by the 20S proteasome, as demonstrated by in vitro reconstitution with purified REGγ, SRC-3, and 20S proteasome. In vitro proteasome proteolysis assay with purified components, RNAi knockdown and overexpression, reporter assay for ER target gene expression Cell High 16439211
2006 AIB1 (NCOA3) is sumoylated, and sumoylation attenuates its transactivation activity; estrogen treatment leads to increased phosphorylation and decreased sumoylation of AIB1; sumoylation and phosphorylation coordinately regulate AIB1 transcriptional output. In vivo sumoylation assay, phosphorylation analysis, reporter assay, Western blot The Journal of biological chemistry Medium 16760465
2006 SRC-3/NCOA3 is phosphorylated by p38MAPK during retinoic acid (RA)-dependent RARα activation; this phosphorylation first facilitates RARα target gene activation by controlling the dynamics of SRC-3/RARα interactions, then promotes SRC-3 degradation to inhibit transcription; phosphorylation and degradation occur specifically within the context of RARα complexes. In vitro kinase assay, p38MAPK inhibitor treatment, Western blot, reporter assay, protein stability assay The EMBO journal Medium 16456540
2006 CARM1 methylates p/CIP (NCOA3) at three conserved arginine residues in a glutamine-rich C-terminal region; CARM1 is the required methyltransferase (not other PRMTs); methylation increases p/CIP turnover by enhanced degradation and impairs p/CIP association with CBP, thereby negatively impacting transcription. In vitro methylation assay, metabolic labeling, mass spectrometry identification of methylation sites, CARM1 knockout MEF extracts, CBP co-immunoprecipitation, methylation site mutants Molecular and cellular biology High 17043108
2008 SRC-3/AIB1 is phosphorylated at C-terminal tyrosine Y1357 by c-Abl kinase; this phosphorylation is induced by IGF-I, EGF, and estrogen and is required for AIB1 coactivation of ERα, PR-B, NF-κB, and AP-1 promoters; Y1357 phosphorylation modulates AIB1 association with c-Abl, ERα, p300, and CARM1. In vitro kinase assay, phospho-specific antibody, co-immunoprecipitation, reporter assay, imatinib inhibitor treatment, cell growth and focus formation assay Molecular and cellular biology High 18765637
2008 SRC-3/AIB1 is required for focal adhesion turnover, focal adhesion kinase activation, and directly regulates transcription of MMP-2 and MMP-13 through coactivation of AP-1 and PEA3, promoting prostate cancer cell migration and invasion. siRNA knockdown, focal adhesion turnover assay, chromatin immunoprecipitation, reporter assay, invasion assay Cancer research Medium 18593949
2008 AIB1 serves as a PEA3 coactivator and forms complexes with PEA3 on MMP2 and MMP9 promoters to enhance their expression in breast cancer cells; AIB1 deficiency reduces lung metastasis in the PyMT mouse model and AIB1-null tumor cells maintain epithelial markers and form polarized acinar structures unlike wild-type tumor cells. Knockout mouse/tumor transplantation model, chromatin immunoprecipitation, reporter assay, 3D culture, invasion assay Molecular and cellular biology High 18644862
2008 ACTR/AIB1 (NCOA3) binds NCBD domain of CBP/p300 through mutual synergistic folding; the free ACTR activation domain (residues 1041-1088) is completely unfolded in isolation but forms a well-ordered helical complex upon binding to CBP; backbone dynamics of the complex are consistent with a fully folded protein. NMR relaxation (15N longitudinal/transverse rates, heteronuclear NOE), secondary chemical shift analysis Biochemistry High 18177052
2008 PP1, PP2A, and PDXP are key negative regulators of SRC-3/AIB1 coactivator activity; PDXP and PP2A dephosphorylate SRC-3 and inhibit its ligand-dependent association with estrogen receptor; PP1 stabilizes SRC-3 by dephosphorylating a phospho-degron at Ser101/Ser102, preventing proteasome-dependent turnover; PP1 regulates SRC-3-dependent cell proliferation and invasion in breast cancer cells. Functional genomic phosphatase screen, in vitro dephosphorylation assay, co-immunoprecipitation, SRC-3 stability assay, cell proliferation and invasion assay Molecular cell High 18922467
2010 SRC3/AIB1 (NCOA3) interacts with hormone-activated androgen receptor via synergistic binding of its first and third LXXLL motifs; crystal structure reveals the molecular basis for AR's preference for SRC3 over other coactivators; AR mutations found in prostate cancer patients correlate with their SRC3 binding potency. Crystal structure determination, mutagenesis, biochemical binding assays, functional transactivation assays The Journal of biological chemistry High 20086010
2010 ATBF1 inhibits estrogen receptor function by selectively competing with AIB1 but not GRIP1 or SRC-1 for binding to ERα; ATBF1 physically interacts with ER via multiple domains in both proteins and inhibits ER-mediated gene transcription and cell growth. In vitro and in vivo co-immunoprecipitation, competitive binding assay, reporter assay, cell proliferation assay The Journal of biological chemistry Medium 20720010
2010 NCOA3 (SRC-3) promotes Ago2 expression at the transcriptional level in hippocampal neurons, thereby stimulating miRNA function; Ncoa3 knockdown reduces dendritic complexity and dendritic spine maturation in a miRNA-dependent manner that can be rescued by Ago2 overexpression. RNAi knockdown, Ago2 overexpression rescue, fluorescence microscopy for dendritic morphology, reporter assays for miRNA function The EMBO journal Medium 26105073
2011 AIB1 (NCOA3) is phosphorylated at Ser728 and Ser867 by CDK1/Cyclin B at the onset of mitosis; this phosphorylation correlates with exclusion of AIB1 from condensed chromatin and redistribution to the cell periphery without affecting its transcriptional properties; PP1 likely mediates dephosphorylation at mitotic exit. In vitro kinase assay, specific kinase inhibitors, phospho-specific antibody, Western blot, fluorescence microscopy, subcellular fractionation, luciferase reporter assay PloS one High 22163316
2012 Ncoa3 interacts with the orphan nuclear receptor Esrrb via its ligand-binding domain and bridges Esrrb to RNA polymerase II complexes; Ncoa3 is required for induction and maintenance of pluripotency in embryonic stem cells and shares genome-wide gene regulatory functions with Esrrb at active enhancers through cooperation with the Oct4-Sox2-Nanog circuitry. Co-immunoprecipitation, ChIP-sequencing, microarray gene expression analysis, RNAi knockdown, ESC self-renewal and differentiation assays Genes & development High 23019124
2012 Ncoa3 binds the Nanog promoter and recruits CBP (histone acetyltransferase) and CARM1 (histone arginine methyltransferase) to activate Nanog expression in mouse ESCs; GSK3 signaling downregulates Ncoa3 protein level to suppress Nanog expression. Chromatin immunoprecipitation, co-immunoprecipitation, RNAi knockdown, reporter assay, Western blot The Journal of biological chemistry Medium 22977234
2012 PIAS1 is the SUMO E3 ligase responsible for AIB1 sumoylation; PIAS1 co-immunoprecipitates with AIB1, and overexpression of wild-type PIAS1 (but not the E3 ligase-dead C350S mutant) increases AIB1 sumoylation, promotes AIB1 stability, represses AIB1 transcriptional activity, and attenuates AIB1 interaction with ERα, reducing cell growth. Co-immunoprecipitation, sumoylation assay, reporter assay, PIAS1 E3 ligase mutant, cell proliferation assay Biology of the cell Medium 22283414
2012 p/CIP (NCOA3) and SRC-1 cooperatively regulate insulin signaling through IRS1: deletion of both coactivators significantly increases IRS1 expression in fat and muscle cells and in vivo, enhancing insulin sensitivity and glucose metabolism. Double knockout mouse model, gene expression analysis, glucose uptake assay, insulin sensitivity testing PloS one Medium 22859932
2013 PTEN interacts with AIB1 via its phosphatase domain and acts as a bridge between AIB1 and the E3 ubiquitin ligase Fbw7α (via PTEN's C2 domain), promoting ubiquitin-mediated degradation of AIB1 in a phosphatase-activity-independent manner, thereby reducing AIB1 transcriptional activity. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, PTEN phosphatase mutant, cell proliferation assay Molecular cancer Medium 23514585
2013 AIB1 cooperates with ERα to promote EMT in breast cancer cells through activation of SNAI1 transcription; AIB1-ERα complex binds ERα-binding sites on the SNAI1 promoter to upregulate SNAI1, which represses E-cadherin expression; this requires an ERα-binding site on SNAI1 promoter. Overexpression and knockdown of AIB1 and SNAI1, E-cadherin expression analysis, migration/invasion assay, promoter analysis PloS one Medium 23762395
2014 NCOA3 regulates MUC4 promoter accessibility (chromatin remodeling) as demonstrated by micrococcal nuclease digestion and ChIP assays; NCOA3 knockdown abrogates retinoic acid-mediated MUC4 upregulation; NCOA3 also stabilizes mucins (MUC4 and MUC1) post-translationally through fucosylation via FUT8. Chromatin immunoprecipitation, micrococcal nuclease digestion assay, siRNA knockdown, gene expression analysis, FUT8 knockdown Oncogene Medium 25531332
2016 NCOA3 is a transcriptional target of XBP1; NCOA3 is required for optimal activation of the PERK-eIF2α-ATF4 pathway during UPR; NCOA3 is required for XBP1 induction during estrogen stimulation, forming a positive feedback loop maintaining high NCOA3 and XBP1 levels in breast cancer cells. RNAi knockdown, reporter assay, Western blot for UPR pathway components, promoter analysis Oncogene Medium 27109102
2018 MAD2L2 (REV7) interacts with NCOA3, and MAD2L2 overexpression suppresses NCOA3 by activating p38 kinase, which phosphorylates NCOA3 and leads to its ubiquitination and proteasomal degradation. Immunoprecipitation/mass spectrometry, co-immunoprecipitation, p38 inhibitor, Western blot for NCOA3 stability, ubiquitination assay, in vitro and in vivo tumor models Molecular oncology Medium 29360267
2018 Cytoplasmic PELP1 forms a complex with AIB1 (NCOA3), elevates AIB1 phosphorylation at Thr24, and promotes cancer stem cell-like (ALDH+) tumorsphere formation; direct manipulation of AIB1 levels or pharmacological inhibition of AIB1 abrogates cytoplasmic PELP1-induced tumorsphere formation. Co-immunoprecipitation, phospho-specific Western blot, shRNA knockdown, tumorsphere/ALDH assay, AIB1 inhibitor (SI-2), syngeneic in vivo tumor model Molecular cancer research Medium 29348189
2009 CK1δ phosphorylates AIB1 at a novel site (S601) and ERα in vitro; CK1δ interacts with ERα and AIB1 in vivo and increases ERα-AIB1 association; CK1δ overexpression promotes AIB1 protein stability in an estradiol-dependent manner; CK1δ silencing reduces ERα transcriptional activity and decreases AIB1 levels via proteasome-mediated degradation. In vitro kinase assay, co-immunoprecipitation, siRNA knockdown, luciferase reporter assay, proteasome inhibitor treatment, Western blot Nucleic acids research Medium 19339517
2021 SRC-3 (NCOA3) is enriched in regulatory T cells (Tregs) in mice and humans; SRC-3 depletion or pharmacological inhibition causes failure of Treg induction from resting T cells and loss of ability to suppress proliferation of stimulated T cells. Bioinformatics analysis of public data, directed cellular assays, pharmacological inhibition, T cell suppression assay Scientific reports Medium 33564037
2009 AIB1 directly interacts with ERRα as demonstrated by FRET, mammalian two-hybrid, and co-immunoprecipitation of endogenous proteins; AIB1 enhances ERRα transcriptional activity in ERα-negative breast cancer cell lines; both proteins are recruited to ERRα target gene promoters; blocking ERRα with an inverse agonist abolishes AIB1-ERRα interaction and coactivation. FRET, mammalian two-hybrid, endogenous co-immunoprecipitation, chromatin immunoprecipitation, reporter assay, inverse agonist treatment Cancer research High 19491275

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science (New York, N.Y.) 1397 9252329
1997 Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 1256 9267036
1997 The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 1100 9192892
2003 Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. Journal of the National Cancer Institute 642 12618500
2000 The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. Proceedings of the National Academy of Sciences of the United States of America 434 10823921
2006 Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Molecular and cellular biology 412 16940181
2000 AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor. Molecular and cellular biology 359 10866661
2004 High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer cell 320 15380517
1997 TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1. The Journal of biological chemistry 316 9346901
2000 Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell 245 11163181
2006 The SRC-3/AIB1 coactivator is degraded in a ubiquitin- and ATP-independent manner by the REGgamma proteasome. Cell 234 16439211
2004 ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. Molecular and cellular biology 233 15169882
2002 Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Molecular and cellular biology 226 11971985
2002 The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Molecular and cellular biology 212 12138202
2008 The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression. Molecular and cellular biology 167 18644862
1999 Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas. The American journal of pathology 158 10027410
2004 AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice. Cancer research 154 14996752
2000 Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers. International journal of cancer 145 10861496
2001 Expression of the nuclear coactivator AIB1 in normal and malignant breast tissue. Breast cancer research and treatment 124 11678305
2004 Coactivator AIB1 links estrogen receptor transcriptional activity and stability. Proceedings of the National Academy of Sciences of the United States of America 113 15289619
2004 Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1. Journal of clinical pathology 112 15452162
2001 AIB1 enhances estrogen-dependent induction of cyclin D1 expression. Cancer research 109 11358796
2006 The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are regulated by CARM1-dependent methylation. Molecular and cellular biology 106 17043108
2005 Associations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 105 15788656
2002 Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1. The Journal of steroid biochemistry and molecular biology 98 12650696
2004 Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during progression of pancreatic adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 96 15448000
2001 Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer research 95 11454686
2008 Steroid receptor coactivator-3/AIB1 promotes cell migration and invasiveness through focal adhesion turnover and matrix metalloproteinase expression. Cancer research 94 18593949
2010 Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. The Journal of biological chemistry 85 20086010
2006 SRC-3/AIB1: transcriptional coactivator in oncogenesis. Acta pharmacologica Sinica 80 16539836
2012 Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming. Genes & development 78 23019124
2008 NMR relaxation study of the complex formed between CBP and the activation domain of the nuclear hormone receptor coactivator ACTR. Biochemistry 76 18177052
2009 The role and regulation of the nuclear receptor co-activator AIB1 in breast cancer. Breast cancer research and treatment 74 19418218
2006 Coordinated regulation of AIB1 transcriptional activity by sumoylation and phosphorylation. The Journal of biological chemistry 73 16760465
2005 Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma. Human pathology 69 16084947
2004 The nuclear receptor coactivator AIB1 mediates insulin-like growth factor I-induced phenotypic changes in human breast cancer cells. Cancer research 69 15548698
2006 P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARalpha-mediated transcription. The EMBO journal 68 16456540
2001 Gene amplification and expression of the steroid receptor coactivator SRC3 (AIB1) in sporadic breast and endometrial carcinomas. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 59 11355743
1993 Localization of activin receptor (ActR-IIB2) mRNA in the rat seminiferous epithelium. Endocrinology 59 8380387
2008 Crystal structures of the Streptomyces coelicolor TetR-like protein ActR alone and in complex with actinorhodin or the actinorhodin biosynthetic precursor (S)-DNPA. Journal of molecular biology 56 18207163
2010 Deregulated E2F and the AAA+ coregulator ANCCA drive proto-oncogene ACTR/AIB1 overexpression in breast cancer. Molecular cancer research : MCR 54 20124470
2016 Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3. Cell death & disease 53 27831559
2010 Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness. Oncogene 53 20305690
2008 Essential phosphatases and a phospho-degron are critical for regulation of SRC-3/AIB1 coactivator function and turnover. Molecular cell 53 18922467
2006 Steroid receptor coactivator AIB1 in endometrial carcinoma, hyperplasia and normal endometrium: Correlation with clinicopathologic parameters and biomarkers. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 51 16980945
2007 Epidermal growth factor receptor (EGFR) and the estrogen receptor modulator amplified in breast cancer (AIB1) for predicting clinical outcome after adjuvant tamoxifen in breast cancer. Breast cancer research and treatment 50 17636398
2008 Tyrosine phosphorylation of the nuclear receptor coactivator AIB1/SRC-3 is enhanced by Abl kinase and is required for its activity in cancer cells. Molecular and cellular biology 49 18765637
2016 NCOA3 coactivator is a transcriptional target of XBP1 and regulates PERK-eIF2α-ATF4 signalling in breast cancer. Oncogene 47 27109102
2010 Estrogen-dependent and estrogen-independent mechanisms contribute to AIB1-mediated tumor formation. Cancer research 47 20442283
2010 The cooperative function of nuclear receptor coactivator 1 (NCOA1) and NCOA3 in placental development and embryo survival. Molecular endocrinology (Baltimore, Md.) 46 20685850
2004 The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6. The Journal of biological chemistry 46 15145939
2000 Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator. Endocrinology 45 10965917
2010 ATBF1 inhibits estrogen receptor (ER) function by selectively competing with AIB1 for binding to the ER in ER-positive breast cancer cells. The Journal of biological chemistry 44 20720010
2015 A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function. The EMBO journal 43 26105073
2012 Role of nuclear receptor coactivator 3 (Ncoa3) in pluripotency maintenance. The Journal of biological chemistry 43 22977234
2005 Association of NCOA3 polymorphisms with breast cancer risk. Clinical cancer research : an official journal of the American Association for Cancer Research 43 15788663
2013 AIB1 cooperates with ERα to promote epithelial mesenchymal transition in breast cancer through SNAI1 activation. PloS one 42 23762395
2006 SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous cell carcinomas. Cancer letters 42 16458427
2006 Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland. Cancer research 41 17145884
2004 Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Delta3 on estrogenic ligands with different intrinsic activity. Oncogene 40 14691461
2002 Polymorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk: a population-based case-control study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 40 11927493
1998 Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that is related to AIB1, p/CIP, and TIF2. Molecular endocrinology (Baltimore, Md.) 40 9658407
2014 NCOA3-mediated upregulation of mucin expression via transcriptional and post-translational changes during the development of pancreatic cancer. Oncogene 39 25531332
2008 Ligand recognition by ActR, a TetR-like regulator of actinorhodin export. Journal of molecular biology 39 18804114
2000 Endogenously expressed estrogen receptor and coactivator AIB1 interact in MCF-7 human breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 39 11050174
2020 Elevated GCN5 expression confers tamoxifen resistance by upregulating AIB1 expression in ER-positive breast cancer. Cancer letters 38 32987137
2012 AIB1:ERα transcriptional activity is selectively enhanced in aromatase inhibitor-resistant breast cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research 38 22550166
2008 Role of AIB1 for tamoxifen resistance in estrogen receptor-positive breast cancer cells. Oncology 38 18827493
2002 Microtubule-dependent subcellular redistribution of the transcriptional coactivator p/CIP. Molecular and cellular biology 38 12192059
2006 ACTR/AIB1/SRC-3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes. The Prostate 37 16921507
2003 The coactivator p/CIP/SRC-3 facilitates retinoic acid receptor signaling via recruitment of GCN5. The Journal of biological chemistry 36 12885766
2014 Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio via AIB1 or SMRT recruitment to the CCND1 and MYC promoters. International journal of cancer 35 25363551
2018 MAD2L2 inhibits colorectal cancer growth by promoting NCOA3 ubiquitination and degradation. Molecular oncology 34 29360267
2007 Proto-oncogene ACTR/AIB1 promotes cancer cell invasion by up-regulating specific matrix metalloproteinase expression. Cancer letters 34 18162290
2003 Clinical significance of AIB1 expression in human breast cancer. Breast cancer research and treatment 34 14503806
2021 Circ_0001667 knockdown blocks cancer progression and attenuates adriamycin resistance by depleting NCOA3 via releasing miR-4458 in breast cancer. Drug development research 33 34227151
2009 AIB1 is a predictive factor for tamoxifen response in premenopausal women. Annals of oncology : official journal of the European Society for Medical Oncology 33 19628566
2004 Polyglutamine repeat length in the AIB1 gene modifies breast cancer susceptibility in BRCA1 carriers. International journal of cancer 33 14648706
2016 Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis. Biomaterials 30 27267632
2009 AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells. Biochemical and biophysical research communications 30 19285025
2001 Detection of antisense and ribozyme accessible sites on native mRNAs: application to NCOA3 mRNA. Molecular therapy : the journal of the American Society of Gene Therapy 30 11708882
2020 NR5A2 synergizes with NCOA3 to induce breast cancer resistance to BET inhibitor by upregulating NRF2 to attenuate ferroptosis. Biochemical and biophysical research communications 29 32536370
2009 Estrogen-related receptor alpha expression and function is associated with the transcriptional coregulator AIB1 in breast carcinoma. Cancer research 29 19491275
2005 AIB1 polymorphisms predict aggressive ovarian cancer phenotype. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 28 16365010
2001 Association of steroid receptor coactivator AIB1 with estrogen receptor-alpha in breast cancer cells. Breast cancer research and treatment 28 11768608
2000 The ActR-I activin receptor protein is expressed in notochord, lens placode and pituitary primordium cells in the mouse embryo. Mechanisms of development 28 10704880
2010 Overexpression of AIB1 negatively affects survival of surgically resected non-small-cell lung cancer patients. Annals of oncology : official journal of the European Society for Medical Oncology 27 20064830
2021 Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs. Scientific reports 26 33564037
2013 NCOA3 is a selective co-activator of estrogen receptor α-mediated transactivation of PLAC1 in MCF-7 breast cancer cells. BMC cancer 26 24304549
2005 The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers. Carcinogenesis 26 16244359
2009 CK1delta modulates the transcriptional activity of ERalpha via AIB1 in an estrogen-dependent manner and regulates ERalpha-AIB1 interactions. Nucleic acids research 25 19339517
2005 Characterization of two candidate genes, NCoA3 and IRF8, potentially involved in the control of HIV-1 latency. Retrovirology 25 16305739
2018 Residual Structure Accelerates Binding of Intrinsically Disordered ACTR by Promoting Efficient Folding upon Encounter. Journal of molecular biology 24 30528464
2011 Phosphorylation of AIB1 at mitosis is regulated by CDK1/CYCLIN B. PloS one 24 22163316
2018 Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models Are Promoted by PELP1/AIB1 Complexes. Molecular cancer research : MCR 23 29348189
2013 AIB1 predicts bladder cancer outcome and promotes bladder cancer cell proliferation through AKT and E2F1. British journal of cancer 22 23511556
2013 PTEN suppresses the oncogenic function of AIB1 through decreasing its protein stability via mechanism involving Fbw7 alpha. Molecular cancer 22 23514585
2012 The transcriptional activity of co-activator AIB1 is regulated by the SUMO E3 ligase PIAS1. Biology of the cell 22 22283414
2012 The transcriptional coactivators p/CIP and SRC-1 control insulin resistance through IRS1 in obesity models. PloS one 22 22859932
2007 Agrobacterium tumefaciens C58 uses ActR and FnrN to control nirK and nor expression. Journal of bacteriology 22 17981975

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