Affinage

NCOA2

Nuclear receptor coactivator 2 · UniProt Q15596

Length
1464 aa
Mass
159.2 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCOA2 (TIF2/SRC-2/GRIP1) is a p160-family transcriptional coactivator that couples liganded nuclear receptors to the general transcription machinery and chromatin-modifying enzymes (PMID:8670870, PMID:9430642). It engages agonist-bound receptor ligand-binding domains through three LxxLL NR-box motifs in an intrinsically disordered receptor-interaction domain that becomes structured upon receptor engagement, with flanking sequences contributing to a multisite binding mode (PMID:9430642, PMID:33647291); its AD1 region transactivates by recruiting CBP/p300 while AD2 acts independently (PMID:9430642). Beyond classical LBD binding, NCOA2 directly binds and increases the α-helical content of the disordered AF1 domain of steroid receptors, and can bridge receptor AF1 and AF2 surfaces to produce synergistic activation (PMID:11265755, PMID:23132854). Context determines its output: NCOA2 also acts as a corepressor at glucocorticoid-repressed genes (PMID:11689447), and integrates upstream signaling through PKA-dependent destabilization (PMID:11923473), mTORC1-dependent phosphorylation (PMID:25664849), and PFKFB4-mediated Ser487 phosphorylation (PMID:33593309). Knockout mice establish non-redundant physiological roles in reproduction (PMID:12138202), adaptive thermogenesis and obesity resistance (PMID:12507421, PMID:21035760), and hepatic glucose homeostasis, where NCOA2 coactivates RORα to control glucose-6-phosphatase and prevents a Von Gierke-like glycogenopathy (PMID:19039140). NCOA2 further serves as a coactivator of the BMAL1:CLOCK circadian oscillator (PMID:24529706) and of SREBP-1 in lipogenesis (PMID:25664849, PMID:26548416), and supports CD8+ T-cell antitumor immunity by CREB-directed recruitment to the PGC-1α enhancer to drive mitochondrial biogenesis (PMID:37540802). In cancer, NCOA2 behaves as both a tumor suppressor (cooperating against MYC-driven liver tumorigenesis) (PMID:22556267, PMID:28273073) and an oncogenic driver, most notably as a recurrent fusion partner: the MOZ-TIF2 fusion transforms hematopoietic progenitors by combining MOZ nucleosomal targeting and HAT activity with TIF2/AD1-mediated CBP recruitment (PMID:9558366, PMID:12676584, PMID:24258712), and fusions with HEY1, ETV6, and PAX3 drive mesenchymal chondrosarcoma, leukemia, and rhabdomyosarcoma respectively (PMID:35342947, PMID:34624096, PMID:24213582).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1996 High

    Established NCOA2 as a bona fide nuclear receptor coactivator, defining the core activity from which all later functions derive — that it binds agonist-bound receptor LBDs and autonomously activates transcription.

    Evidence Cloning with yeast two-hybrid, in vitro LBD binding, and mammalian reporter assays

    PMID:8670870

    Open questions at the time
    • Did not map the binding motifs or the activation domains
    • No endogenous target genes identified
  2. 1998 High

    Resolved the molecular grammar of receptor engagement and transactivation by mapping three LxxLL NR-boxes for receptor binding and separating AD1 (CBP-dependent) from AD2 (CBP-independent) activation surfaces.

    Evidence Systematic NR-box mutagenesis, two-hybrid, reporter and dominant-negative peptide assays across two studies

    PMID:9430642 PMID:9742117

    Open questions at the time
    • Structural basis of NR-box selectivity not resolved
    • How AD2 activates transcription mechanistically unknown
  3. 1998 High

    Connected coactivator recruitment to receptor surface integrity and identified the oncogenic MOZ-TIF2 fusion, framing both physiological AF-2 dependence and a disease-relevant rearrangement.

    Evidence AR AF-2 residue mutagenesis (E888) plus FISH/RT-PCR characterization of inv(8) fusion

    PMID:9558366 PMID:9717843

    Open questions at the time
    • Fusion oncogenicity not functionally tested at this stage
    • AF-2 contact mode inferred from mutants only
  4. 2000 High

    Showed NCOA2 bridges receptor AF1 and AF2 domains to drive synergy, extending its action beyond LBD docking and revealing isotype-selective, p160-non-redundant bridging.

    Evidence Mammalian two-hybrid, in vitro binding, and domain-selective mutants on ERα and RARα1

    PMID:11265755 PMID:12149266

    Open questions at the time
    • Structural mechanism of dual-domain bridging unresolved
    • Generality across receptors untested
  5. 2001 High

    Demonstrated NCOA2 can act as a corepressor at specific glucocorticoid-repressed genes, establishing that its transcriptional output is context-dependent rather than uniformly activating.

    Evidence ChIP, reporter and dominant-negative mutant analysis at the col3A response element

    PMID:11689447

    Open questions at the time
    • Repression mechanism / partner enzymes not defined
    • Promoter determinants of activator-vs-repressor switch unknown
  6. 2002 High

    Defined upstream signal control and the first physiological roles, showing PKA destabilizes NCOA2 via AD2 and that loss in mice produces distinct reproductive and metabolic phenotypes.

    Evidence PKA cotransfection with domain deletions; TIF2-null mouse reproductive and metabolic phenotyping with co-IP of SRC-1/PGC-1α

    PMID:11923473 PMID:12138202 PMID:12507421

    Open questions at the time
    • PKA does not phosphorylate a defined NCOA2 residue here
    • Tissue-specific target genes not fully resolved
  7. 2003 High

    Proved MOZ-TIF2 is leukemogenic in vivo and dissected the required modules — MOZ nucleosome recognition plus TIF2/AD1-mediated CBP recruitment — converting an associative fusion into a mechanistic oncogene.

    Evidence Murine bone marrow transplant AML model with systematic domain-deletion mutants; β-catenin/AR/TIF2 three-way complex by co-IP and two-hybrid

    PMID:12588987 PMID:12676584

    Open questions at the time
    • Direct target genes of MOZ-TIF2 not yet identified at this stage
    • MOZ HAT role appeared dispensable here but revisited later
  8. 2004 High

    Established p160 functional redundancy and a nuclear-compartment model, showing SRC-1 compensates in Sertoli cells and that TIF2 forms pre-assembled foci that recruit GR and coactivators upon ligand.

    Evidence SRC-1/TIF2 compound-mutant mice; immunofluorescence/live imaging with microinjected GRE

    PMID:15070739 PMID:15207724

    Open questions at the time
    • Molecular basis of foci formation undefined
    • Degree of redundancy across other tissues unknown
  9. 2005 High

    Clarified the dominant-negative mechanism of MOZ-TIF2 and a β-catenin bridging route, showing the fusion sequesters CBP via AD1 and depletes it from PML bodies.

    Evidence Reciprocal co-IP, FRET, immunofluorescence and reporter assays; β-catenin/TIF2/AR co-IP and dominant-negative peptide

    PMID:15657427 PMID:16141201

    Open questions at the time
    • How CBP sequestration translates to specific gene deregulation unresolved
    • β-catenin bridging significance in vivo untested
  10. 2007 Medium

    Identified accessory regulators and a corepressor-competition mechanism, showing an N-terminal NCOA2 fragment competes with NCoR/SMRT for receptor binding and that STAMP/TTLL5 modulates NCOA2 output.

    Evidence Two-hybrid, pulldown, co-IP, ChIP, siRNA of endogenous STAMP, NCoR mutagenesis (two studies)

    PMID:17116691 PMID:17571860

    Open questions at the time
    • Functional significance of NCoR competition at endogenous genes limited
    • STAMP/TTLL5 enzymatic contribution to NCOA2 regulation unclear
  11. 2008 High

    Defined a discrete metabolic function in hepatic glucose release, linking NCOA2 to RORα coactivation of G6Pase and revealing a glycogenopathy phenotype on its loss.

    Evidence Whole-body and liver-specific knockout mice with metabolic phenotyping, RORα coactivation and ChIP

    PMID:19039140

    Open questions at the time
    • Full hepatic complex composition not yet mapped
    • Signal that activates NCOA2 during fasting undefined here
  12. 2010 High

    Extended the muscle/metabolism axis and the leukemia mechanism, showing TIF2 antagonizes SRC-1/UCP3 in muscle and that MOZ-TIF2 requires PU.1 to drive CSF1R for leukemia stem-cell maintenance.

    Evidence Inducible muscle-specific knockout with metabolic phenotyping; co-IP, PU.1-deficient mice, CSF1R inhibitor, serial transplantation

    PMID:20418886 PMID:21035760

    Open questions at the time
    • Mechanism of SRC-1/TIF2 antagonism at UCP3 not fully defined
    • How PU.1 cooperates structurally with the fusion unknown
  13. 2012 High

    Defined NCOA2's role in adipogenesis and the biophysics of AF1 engagement, showing it can directly fold the disordered GR AF1 and that it suppresses inhibitory PPARγ-S114 phosphorylation; also revealed a tumor-suppressor role in liver.

    Evidence siRNA single-cell adipocyte assays; CD and HDX-MS on GR AF1; cardiac and Sleeping Beauty/MYC liver tumor models

    PMID:21220509 PMID:22556267 PMID:23132854 PMID:23300926

    Open questions at the time
    • Structural detail of the NCOA2-AF1 complex not at residue resolution
    • Tumor-suppressor target genes not yet identified at this stage
  14. 2013 High

    Refined MOZ-TIF2 leukemogenesis to require MOZ HAT activity via a BRPF1-containing complex at HOX genes, and identified PAX3-NCOA2 as a rhabdomyosarcoma driver.

    Evidence Co-IP, ChIP, shRNA, HAT-mutant fusion and AML model; PAX3-NCOA2 cell-line and xenograft assays

    PMID:24213582 PMID:24258712

    Open questions at the time
    • Reconciliation with earlier HAT-dispensable finding context-dependent
    • PAX3-NCOA2 endogenous target genes not mapped
  15. 2014 High

    Established NCOA2 as a circadian and oncogenic metabolic hub, coactivating BMAL1:CLOCK genome-wide and, downstream of mTORC1, SREBP-1 to drive glutamine-fueled lipogenesis and prostate cancer.

    Evidence ChIP-seq with KO behavioral/metabolomic phenotyping; isotope tracing, co-IP, xenografts and prostate GOF/LOF mouse models

    PMID:24529706 PMID:25295534 PMID:25664849

    Open questions at the time
    • mTORC1-phosphorylated NCOA2 residue not pinpointed here
    • Crosstalk between circadian and lipogenic programs unexplored
  16. 2015 Medium

    Expanded NCOA2's regulatory range to Wnt/β-catenin suppression, SREBP-1-driven lipid/glucose genes (metformin target), and HIF-1α/AhR competition controlling angiogenesis.

    Evidence GOF/LOF reporter, ChIP and xenograft assays across colorectal, hepatic and angiogenesis models

    PMID:25823027 PMID:26350169 PMID:26487680 PMID:26548416

    Open questions at the time
    • Direct vs indirect pathway effects not always separated
    • Mechanism of ARNT-competition not structurally defined
  17. 2017 High

    Identified the direct anti-tumorigenic target genes (SHP, DKK4, CADM4) through which NCOA2 suppresses MYC-driven liver cancer, giving molecular substance to its tumor-suppressor role.

    Evidence In vivo ChIP-seq, RNA-seq, KO tumor model and functional rescue with individual target genes

    PMID:28273073

    Open questions at the time
    • Receptor/partner directing NCOA2 to these promoters not defined
    • Why the same coactivator is oncogenic elsewhere unresolved
  18. 2018 Medium

    Defined the decidualization transcriptome and refined leukemic fusion mechanism, showing NCOA2 is required for full PGR response in endometrium and that ETV6-NCOA2 recruits p300 to derepress ETV6 targets.

    Evidence ChIP-seq/RNA-seq with siRNA in primary hESCs; co-IP, ChIP and mouse/human leukemia models; Ring1A/B-Glis2 epistasis in AML

    PMID:29371181 PMID:30325183 PMID:34624096

    Open questions at the time
    • NOTCH1 cooperativity mechanism with ETV6-NCOA2 incomplete
    • PRC1 link to NCOA2-fusion chromatin state indirect
  19. 2019 High

    Revealed a non-transcriptional, virology role: NCOA2 stabilizes the KSHV RTA protein by competing with MDM2, promoting lytic reactivation through a positive feedback loop.

    Evidence In vitro and in vivo co-IP, MDM2 competition and proteasome assays, GOF/LOF in infected cells

    PMID:31751430

    Open questions at the time
    • Whether NCOA2 stabilizes other clients similarly unknown
    • Structural basis of PARS II binding not resolved
  20. 2021 High

    Pinpointed signaling control and the disordered structural basis of receptor recognition, identifying PFKFB4-mediated Ser487 phosphorylation and resolving the multisite NR-box binding mode by NMR/crystallography.

    Evidence Co-IP, phospho-Ser487 immunoblot and functional assays; NMR, SAXS, X-ray and SEC-MALS of TIF2NRID with RXR/RAR

    PMID:33593309 PMID:33647291

    Open questions at the time
    • Functional consequence of disorder-to-order transition in cells untested
    • How distinct phosphorylations integrate combinatorially unknown
  21. 2022 High

    Mechanistically resolved the HEY1-NCOA2 chondrosarcoma fusion, showing it occupies canonical HEY1 promoters and upregulates PDGFB/PDGFRA to activate AKT signaling.

    Evidence ChIP-seq, RNA-seq, inducible iPSC-derived MSC model and phospho-AKT immunoblot

    PMID:35342947

    Open questions at the time
    • NCOA2 moiety's coactivator contribution to fusion activity not isolated
    • Therapeutic targetability of the PDGF axis untested here
  22. 2023 High

    Defined NCOA2's role in immunometabolism and chondrosarcoma in vivo, showing CREB-directed recruitment to the PGC-1α enhancer drives CD8+ T-cell mitochondrial biogenesis and that HEY1-NCOA2 cooperates with Runx2, an HDAC-inhibitor-sensitive program.

    Evidence T-cell conditional KO with ChIP, mitochondrial assays, adoptive transfer and PGC-1α rescue; mouse chondrosarcoma model with co-IP, ChIP-seq, Runx2 KO and panobinostat

    PMID:37212282 PMID:37540802

    Open questions at the time
    • Nuclear receptor partner in the T-cell PGC-1α axis not identified
    • Runx2-independent fusion programs incompletely defined
  23. 2024 High

    Confirmed KAT6 enzymatic dependence of MOZ-TIF2 AML and linked the fusion to histone H3K23 propionylation at a small set of developmental transcription factor genes, defining a druggable enzymatic node.

    Evidence Pharmacological KAT6 inhibition and PROTAC degradation, H3K23pr profiling, ChIP and gene expression analysis

    PMID:38889153

    Open questions at the time
    • Functional role of H3K23pr versus acetylation not separated
    • Which target genes are the essential drivers undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single coactivator integrates its many phosphorylation inputs (PKA, mTORC1, PFKFB4) and partner contexts to switch between activator, corepressor, tumor-suppressor and oncogenic-fusion behaviors at specific loci.
  • No unified model linking post-translational state to genomic target selection
  • Structural basis of context-dependent activator/repressor switching unknown
  • Endogenous full coactivator complex composition across tissues incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9909396 Circadian clock 1
Partners
ARBMAL1CREBBPCTNNB1EP300ESR1SREBF1TTLL5
Complex memberships
BMAL1:CLOCK coactivator complexETV6-NCOA2/p300 complexMOZ-TIF2/BRPF1 complex

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TIF2 (NCOA2) was cloned as a 160 kDa nuclear protein that interacts with nuclear receptors (NRs) in an agonist-dependent manner in vivo, binds directly to NR ligand-binding domains (LBDs) in an agonist- and AF-2-integrity-dependent manner in vitro, harbors an autonomous transcriptional activation function, relieves NR autosquelching, and enhances AF-2 activity when overexpressed in mammalian cells. Yeast two-hybrid, in vitro binding assays, mammalian transfection/reporter assays, co-immunoprecipitation The EMBO journal High 8670870
1998 The TIF2 NR interaction domain (NID) contains three NR-box LxxLL motifs (boxes I, II, III); mutation of all three abrogates NR interaction and AF-2 stimulation. Box II alone is sufficient for efficient interaction with NR holo-LBDs. TIF2 activation domain AD1 mediates transactivation through CBP interaction, whereas AD2 acts independently of CBP. Mutational analysis, mammalian two-hybrid, yeast two-hybrid, transfection/reporter assays, dominant-negative peptide experiments The EMBO journal High 9430642
1998 All three NR boxes (LxxLL motifs) in the TIF2 receptor interaction domain (RID) are necessary and sufficient for interaction with nuclear hormone receptors; individual boxes show receptor-binding preferences. Cooperative binding of two TIF2 molecules to a heterodimeric NR complex occurs even when only one cognate ligand is present, indicating an allosteric effect. NR-box mutagenesis, in vitro binding assays, competition assays, pulldown experiments Molecular and cellular biology High 9742117
1998 The AF-2 activation domain core region of the androgen receptor (AR), specifically residue E888, is required for functional interaction with TIF2; the E888Q mutation markedly reduces TIF2-stimulated AR AF-2 activity without affecting hormone binding or LBD homodimerization. Mammalian cotransfection/reporter assays, yeast two-hybrid, site-directed mutagenesis Molecular endocrinology High 9717843
1998 MOZ-TIF2 fusion protein arises from inv(8)(p11q13) in AML; the predicted fusion retains MOZ histone acetyltransferase homology domains and the CBP-binding domain of TIF2, suggesting that aberrant recruitment of CBP by MOZ-TIF2 underlies the leukemia phenotype. FISH, Southern blotting, RT-PCR, structural analysis of fusion protein Blood Medium 9558366
1999 An AR mutation (M886V) in the LBD disrupts interdomain interactions (LBD–LBD, LBD–NTD) and impairs TIF2 binding, resulting in ~50% reduced transactivation capacity without altering ligand binding. The synthetic androgen mesterolone restores mutant LBD interactions with both the NTD and TIF2. Mammalian two-hybrid, yeast two-hybrid, reporter assays in multiple cell lines, steroid-binding assays The Journal of clinical investigation High 10359561
2000 TIF2 simultaneously interacts with both the isolated N-terminal AF1 domain and the C-terminal AF2 domain of ERα in transfected mammalian cells and in vitro, bridging both receptor domains to produce synergistic transcriptional activation. TIF2 mutants selectively deficient in AF1 or AF2 interaction were used to dissect the contributions of each AF. Mammalian two-hybrid, in vitro binding, reporter gene assays, TIF2 domain-selective mutants EMBO reports High 11265755
2000 AR mutation N727K in the LBD disrupts LBD interactions with the AR TAD and with TIF2 in mammalian and yeast two-hybrid assays, reducing transactivation to ~50% of wild-type without altering ligand binding; mesterolone (but not DHT) restores these interactions. Mammalian two-hybrid, yeast two-hybrid, reporter assays, steroid-binding assays Molecular endocrinology Medium 10935543
2001 TIF2/GRIP1 functions as a corepressor (not only coactivator) at the collagenase-3 col3A response element: it is recruited to col3A and potentiates GR-mediated repression in the presence of GR agonist. GRIP1 mutants deficient in GR binding and coactivator functions were also defective for corepression; a GRIP1 fragment containing the GR-interacting region acted as a dominant-negative for repression. Repression by TR was unaffected by GRIP1. Chromatin immunoprecipitation, reporter assays, dominant-negative mutant analysis, co-factor recruitment assays The EMBO journal High 11689447
2002 PKA activation selectively down-regulates TIF2 protein levels (not mRNA) and impairs its coactivation of nuclear receptors including PPARα/γ and LXRα; the C-terminal activation domain AD2 of TIF2 is required for this inhibitory effect, suggesting AD2 is the target of PKA-mediated down-regulation. Transfection/reporter assays, Western blot, Northern blot, cotransfection with PKA catalytic subunit, TIF2 domain deletions Molecular endocrinology Medium 11923473
2002 TIF2 mediates synergy between RARα1 AF-1 and AF-2 activation functions by bridging both domains; this interaction requires a motif in RARα1 region A and TIF2 AD1. Bridging is RAR isotype-selective (only RARα1) and not observed with SRC-1, demonstrating functional non-redundancy within the p160 family. Mammalian two-hybrid, reporter assays, domain-selective mutants The Journal of biological chemistry Medium 12149266
2002 TIF2-deficient (TIF2−/−) mice are viable but display male hypofertility due to spermiogenesis defects (teratozoospermia) and age-dependent testicular degeneration from defective Sertoli cell–germ cell adhesion, and female hypofertility from placental hypoplasia in decidua stromal cells—demonstrating distinct, non-redundant physiological roles compared to SRC-1 and p/CIP knockouts. Targeted gene knockout (TIF2−/− mice), histological and reproductive phenotype analysis Molecular and cellular biology High 12138202
2002 TIF2−/− mice are protected against obesity and display enhanced adaptive thermogenesis. In white adipose tissue, lack of TIF2 decreases PPARγ activity and reduces fat accumulation; in brown adipose tissue, it facilitates the SRC-1–PGC-1α interaction that induces PGC-1α thermogenic activity. A high-fat diet increases the TIF2/SRC-1 ratio, contributing to weight gain. Knockout mouse model, metabolic phenotyping, co-immunoprecipitation of SRC-1 and PGC-1α, reporter assays Cell High 12507421
2003 MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant model. The C2HC nucleosome recognition motif of MOZ is essential for transformation (MOZ HAT activity is dispensable), and TIF2-mediated interaction with CBP through the TIF2 CBP interaction domain (CID/AD1) is essential for transformation—demonstrating that nucleosomal targeting by MOZ plus CBP recruitment by TIF2 are both required. Murine bone marrow transplant assay, in vitro transformation (colony formation), domain-deletion mutants of MOZ-TIF2 Cancer cell High 12676584
2003 β-catenin binds to the AR ligand-binding domain (AF-2 region) in a ligand agonist-dependent manner, independently of and cooperatively with TIF2 and the AR NTD (both of which also bind AF-2). AR, β-catenin, and TIF2 form a three-way interaction that mediates ligand-dependent transcription; distinct helix-12 mutations selectively disrupt β-catenin but not TIF2/NTD binding. Mammalian two-hybrid, co-immunoprecipitation, reporter gene assays, mutagenesis Molecular and cellular biology High 12588987
2004 SRC-1 partially compensates for TIF2 loss in survival and growth; in Sertoli cells, SRC-1 and TIF2 perform redundant functions—inactivation of SRC-1 alleles in TIF2-null background uniformly accelerates and worsens testicular degeneration, establishing functional redundancy in this cell type. SRC-1/TIF2 compound-mutant mouse analysis, histological and reproductive phenotype characterization Proceedings of the National Academy of Sciences of the United States of America High 15070739
2004 TIF2 forms nuclear foci in the absence of glucocorticoid receptor (GR); upon GR agonist (but not antagonist) treatment, GR is recruited to TIF2 foci. Coactivators p300 and PCAF are also recruited to TIF2 foci, and a microinjected GR-responsive element (GRE) is recruited to these foci—suggesting TIF2 provides a pre-formed nuclear compartment for GR transcriptional complex assembly. Immunofluorescence/live imaging, microinjection of fluorescent GRE, nuclear fractionation Biochemical and biophysical research communications Medium 15207724
2005 MOZ-TIF2 acts as a dominant inhibitor of CBP-dependent transcriptional activators (nuclear receptors, p53). This requires the TIF2 CBP-binding domain (AD1); co-IP and FRET show MOZ-TIF2 interacts with CBP directly in vivo. MOZ-TIF2 displays aberrant nuclear distribution, reduces cellular CBP levels, and depletes CBP from PML bodies. Co-immunoprecipitation, FRET, reporter assays, immunofluorescence, Western blot Molecular and cellular biology High 15657427
2005 β-catenin binds directly to TIF2/GRIP1 (both N- and C-terminal regions of β-catenin required), and β-catenin can mediate binding between TIF2 and AR in a three-way complex. A β-catenin C-terminal peptide (229 aa) binds both TIF2 and AR but acts as a dominant inhibitor of ligand-dependent transcription. Co-immunoprecipitation, mammalian two-hybrid, reporter assays, dominant-negative peptide The Journal of biological chemistry Medium 16141201
2006 STAMP (TTLL5), a newly identified 1,277-aa protein, associates with TIF2 (and SRC-1), is selective for a subset of steroid/nuclear receptors including GR, and modulates TIF2 effects in both GR-mediated gene induction and repression. Endogenous STAMP colocalizes with GR in intact cells and is recruited to promoters of GR-regulated genes. Co-immunoprecipitation, siRNA knockdown of endogenous genes, ChIP, transfection/reporter assays, immunofluorescence Molecular and cellular biology High 17116691
2007 An N-terminal fragment of TIF2 (TIF2.0, aa 1–627) competes with corepressors NCoR/SMRT for binding to GR and PR. This TIF2 N-terminal region binds an N-terminal GR region; for PR-B an N-terminal sequence largely absent in PR-A is necessary but not sufficient. NCoR RID#1 (not RID#2) is required for binding to both GR and PR agonist/antagonist complexes. ChIP shows exogenous TIF2.0 reduces PRE-associated NCoR. Mammalian two-hybrid, pulldown, co-immunoprecipitation, ChIP, NCoR mutagenesis Biochemistry Medium 17571860
2008 Absence of SRC-2 (NCOA2) in mice causes a glycogenopathy resembling Von Gierke's disease. SRC-2 controls fasting hepatic glucose release by coactivating the orphan nuclear receptor RORα to regulate glucose-6-phosphatase (G6Pase) expression; both whole-body and liver-specific SRC-2 ablation produce this phenotype. Whole-body and liver-specific knockout mice, metabolic phenotyping, reporter/coactivation assays with RORα, ChIP Science High 19039140
2009 IL-6-treated LNCaP cells upregulate TIF2 levels and become resistant to bicalutamide. ShRNA knockdown of TIF2 in IL-6-treated cells re-sensitizes them to bicalutamide, while TIF2 overexpression in parental cells confers resistance. IL-6/TIF2 attenuates bicalutamide-mediated blockade of androgen-induced AR nuclear translocation and chromatin recruitment. shRNA knockdown, overexpression, nuclear translocation assay, ChIP, cell viability assays Molecular cancer therapeutics Medium 19240160
2009 cAMP/PKA signaling enhances ERRα interaction with SRC-2 at the SP-A promoter in lung type II cells. SRC-2 has the most pronounced effect among tested coactivators in increasing ERRα transcriptional activity at the SP-A promoter; this is enhanced by PKA catalytic subunit. Three ERRα serines (S87, S114, S277) are critical for PKA and SRC-2 induction of ERRα activity. Reporter assays, co-immunoprecipitation, ChIP, site-directed mutagenesis, pharmacological inhibitors Molecular endocrinology Medium 19264843
2010 MOZ-TIF2 and MOZ-CBP fusion proteins interact with the transcription factor PU.1 to stimulate CSF1R (M-CSFR) expression; PU.1 is essential for MOZ-TIF2 to establish and maintain AML stem cells. Cells with high CSF1R expression contain the leukemia-initiating activity, and CSF1R inhibitors slow MOZ-TIF2-induced leukemia progression. Co-immunoprecipitation, PU.1-deficient mouse studies, transgenic suicide-gene mouse model, CSF1R inhibitor treatment, serial transplantation Nature medicine High 20418886
2010 Conditional ablation of TIF2 in skeletal muscle myofibers (TIF2(i)skm−/− mice) increases mitochondrial uncoupling, protects against sedentariness-induced metabolic decline, delays type 2 diabetes, and attenuates diet-induced obesity. SRC-1 and TIF2 antagonistically modulate UCP3 expression in skeletal muscle: loss of TIF2 elevates SRC-1, which upregulates UCP3. Conditional knockout mice (inducible, muscle-specific), metabolic and mitochondrial phenotyping, gene expression analysis Cell metabolism High 21035760
2011 SRC-2 and SRC-3 (but not SRC-1) are required for human adipocyte differentiation: knockdown of SRC-2 or SRC-3 (individually or jointly) inhibits lipid accumulation and lipogenic gene expression without affecting PPARγ protein levels. SRC-2/SRC-3 knockdown increases inhibitory PPARγ-S114 phosphorylation, revealing a mechanism by which these coactivators promote adipogenesis. siRNA knockdown, high-content analysis (single-cell quantification), lipid staining, phospho-PPARγ immunofluorescence The Journal of cell biology Medium 21220509
2012 The N-terminal fragment of TIF2 (TIF2.0) binds the intrinsically disordered GR AF1 domain, increasing its α-helical content. TIF2 coactivator activity is observed in the absence of the GR LBD in an AF1-dependent manner, establishing that TIF2 can directly modify AF1 structure and activity without requiring LBD interaction. Circular dichroism, hydrogen-deuterium exchange mass spectrometry, cell-based reporter assays, domain-deletion constructs The Journal of biological chemistry High 23132854
2012 SRC-2 ablation activates the 'fetal gene program' in adult mouse heart (shifts in metabolic and sarcomeric gene expression). SRC-2 knockout mice exhibit decreased functional reserve under pressure overload (transverse aortic constriction), blunted ventricular hypertrophic response, and impaired hypertrophic signaling. Knockout mice, genome-wide microarray, targeted gene expression, echocardiography, transverse aortic constriction model PloS one Medium 23300926
2012 Transposon mutagenesis screen (Sleeping Beauty) identified Ncoa2/Src-2 as a tumor suppressor cooperating with MYC in liver cancer. RNAi-mediated knockdown of Ncoa2 in liver progenitor cells accelerates tumor development, and Ncoa2 deletion in mice predisposes to diethylnitrosamine-induced liver tumorigenesis. Sleeping Beauty transposon mutagenesis screen, RNAi knockdown, carcinogen-induced tumorigenesis in KO mice Proceedings of the National Academy of Sciences of the United States of America Medium 22556267
2013 PAX3-NCOA2 fusion protein promotes proliferation and inhibits myogenic differentiation of rhabdomyosarcoma cells. In C2C12 cells, PAX3-NCOA2 accelerates G1/S progression, increases motility, enhances anchorage-independent growth, and increases transcriptional activation of PAX3 consensus-binding sites, but causes weaker differentiation block than PAX3-FOXO1A. Stable cell line expression, proliferation/motility/anchorage-independence assays, cell cycle analysis, reporter assays, nude mouse xenograft Oncogene Medium 24213582
2013 MOZ-TIF2 forms a stable complex with BRPF1 (a component of the MOZ complex); MOZ-TIF2 and BRPF1 co-occupy HOX gene promoters in AML cells. BRPF1 depletion reduces MOZ localization on HOX genes and abolishes MOZ-TIF2 transformation. MOZ-TIF2 lacking HAT activity cannot deregulate HOX genes or initiate leukemia, establishing that MOZ HAT-dependent histone acetylation via the MOZ-TIF2/BRPF1 complex is required for HOX upregulation and AML. Co-immunoprecipitation, ChIP, shRNA depletion, HAT-mutant MOZ-TIF2, colony-forming assay, AML mouse model International journal of hematology High 24258712
2014 SRC-2 (NCOA2) drives glutamine-dependent de novo lipogenesis in prostate cancer cells via reductive carboxylation of α-ketoglutarate through retrograde TCA cycling. Glutamine-mediated mTORC1 signaling activates SRC-2 through mTORC1-dependent phosphorylation; activated SRC-2 then coactivates SREBP-1 to enhance lipogenic enzyme expression. Metabolic profiling (isotope tracing), co-immunoprecipitation (SRC-2/SREBP-1), siRNA/shRNA knockdown, murine tumor xenograft models, ChIP The Journal of clinical investigation High 25664849
2014 Androgen deprivation induces NCoA2 (SRC-2) expression; NCoA2 overexpression in murine prostate causes neoplasia and, combined with PTEN deletion, promotes metastasis-prone cancer. NCoA2 overexpression in prostate tumors results in hyperactivation of PI3K/AKT and MAPK signaling. NCoA2 depletion in PTEN-deficient mice prevents CRPC development. Conditional transgenic overexpression, conditional KO (NCoA2 depletion in PTEN-null mice), signaling pathway analysis (Western blot), human tissue correlation The Journal of clinical investigation High 25295534
2014 SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK heterodimer in the mammalian circadian clock. Genome-wide ChIP shows diurnal SRC-2 recruitment that extensively overlaps with the BMAL1 cistrome. SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in peripheral tissues, disrupts rhythmicity of the hepatic metabolome, and SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Genome-wide ChIP-seq, SRC-2 knockout mice, behavioral assays, metabolomic profiling Cell reports High 24529706
2015 NCOA2 inhibits Wnt/β-catenin signaling in colorectal cancer by simultaneously upregulating inhibitors and downregulating stimulators of the Wnt/β-catenin pathway. Enforced expression of wild-type NCOA2 (but not the LACTB2-NCOA2 fusion protein) impairs pro-tumorigenic phenotypes, whereas NCOA2 knockdown in normal colonocytes has opposite effects. Forced expression and shRNA knockdown, reporter assays, colony formation, xenograft Oncogene Medium 25823027
2015 Metformin transcriptionally suppresses SRC-2 mRNA, reducing SRC-2 and RNA polymerase II recruitment to the G6Pc promoter and to SRE-containing promoters of lipid/cholesterol biosynthesis genes. SRC-2 is identified as a coactivator of SREBP-1 at the FASN promoter via transactivation assays. Reporter/transactivation assays, ChIP, microarray, qRT-PCR, knockdown Scientific reports Medium 26548416
2015 NcoA2 inhibits HIF-1α activation via AhR. NcoA2 overexpression downregulates HRE transactivation by competing with HIF-1α and AhR to form protein complexes with ARNT. NcoA2 knockdown also inhibits HRE transactivation. NcoA2 and HIF-1α nuclear localization decrease in AhR-knockdown cells, and NcoA2 regulates angiogenesis in vitro and in vivo. Reporter assays, co-immunoprecipitation, knockdown/overexpression, in vitro tube formation assay, in vivo plug assay, immunofluorescence Toxicological sciences Medium 26350169
2015 SRC-2 orchestrates transcriptional complexes controlling rate-limiting steps of hepatic glucose release and accretion. DNA pull-down coupled with mass spectrometry identified SRC-2 as an integrator of nutritionally responsive transcriptional complexes; SRC-2 modulates both glucose storage (glycogen) and release programs in liver. DNA pull-down with mass spectrometry, ChIP, reporter assays, KO mouse metabolic phenotyping Proceedings of the National Academy of Sciences of the United States of America Medium 26487680
2017 SRC-2 directly activates a set of anti-tumorigenic target genes (SHP, DKK4, CADM4) that suppress MYC-driven liver tumorigenesis. In vivo ChIP-seq in Src-2−/−/MYC liver tumors shows reduced SRC-2 occupancy at these gene promoters; enforced expression of SHP, DKK4, or CADM4 suppresses tumorigenesis in vitro and in vivo. ChIP-seq, RNA-seq, KO mouse tumor model, in vitro and in vivo functional rescue experiments PLoS genetics High 28273073
2018 Ring1A and Ring1B (PRC1 components) maintain MOZ-TIF2 AML stem cells by repressing Glis2 expression. Deletion of Ring1A/B from MOZ-TIF2 AML cells diminishes self-renewal and induces Glis2 expression; Glis2 overexpression drives differentiation of MOZ-TIF2 AML cells, while Glis2 knockdown in Ring1A/B-deficient cells inhibits differentiation. Conditional deletion of Ring1A/B in mouse AML model, gene expression analysis, Glis2 overexpression/knockdown, colony-forming and differentiation assays Blood Medium 29371181
2018 SRC-2 is required for the full transcriptional response to progesterone receptor (PGR) during human endometrial stromal cell (hESC) decidualization. ChIP-seq and RNA-seq identify the SRC-2-dependent decidualization transcriptome; >50% of SRC-2-regulated genes are also PGR-regulated. SRC-2 is specifically required for induction of the retinol transporter STRA6 during decidualization. ChIP-seq, RNA-seq, siRNA knockdown in primary hESCs, reporter assays Reproduction Medium 30325183
2019 NCOA2 physically interacts with the KSHV replication and transcription activator (RTA) in vitro and in vivo, binding the PARS II domain of RTA. NCOA2 enhances RTA protein stability by competing with the E3 ubiquitin ligase MDM2 for PARS II binding, preventing proteasome-mediated RTA degradation and promoting KSHV lytic reactivation. RTA in turn upregulates NCOA2 expression, forming a positive feedback loop. Co-immunoprecipitation, in vitro binding assay, proteasome inhibition assay, overexpression/knockdown in KSHV-infected cells, lytic gene expression analysis PLoS pathogens High 31751430
2021 PFKFB4 phosphorylates SRC-2 at Ser487, altering SRC-2 transcriptional activity. Co-immunoprecipitation demonstrates PFKFB4–SRC-2 interaction. PFKFB4-mediated SRC-2 phosphorylation promotes lung adenocarcinoma cell proliferation, migration, and invasion; downstream transcriptomics identifies CARM1 as a transcriptional target of SRC-2 involved in this axis. Co-immunoprecipitation, Western blot (phospho-Ser487), siRNA knockdown, overexpression, transcriptome sequencing, cell proliferation/migration/invasion assays BMC pulmonary medicine Medium 33593309
2021 NMR and X-ray crystallographic data reveal that the TIF2 nuclear receptor interaction domain (TIF2NRID) is largely disordered with partially structured NR-box regions. All three NR-boxes and their flanking regions engage RXR/RAR in a multisite binding mode, with flanking regions playing an active role; the protein adopts a more structured conformation upon receptor binding. NMR, SAXS, X-ray crystallography, SEC-MALS, Far-UV CD — structural characterization of TIF2NRID alone and in complex with RXR/RAR Journal of molecular biology High 33647291
2022 HEY1-NCOA2 fusion protein preferentially binds to promoter regions of canonical HEY1 targets (as determined by ChIP-seq), resulting in transactivation of these targets and significant enhancement of cell proliferation in iPSC-derived MSCs. HEY1-NCOA2 (but not wild-type HEY1 or NCOA2 alone) directly targets and upregulates PDGFB and PDGFRA, dramatically increasing phospho-AKT (Ser473). ChIP-seq, RNA-seq, iPSC-derived MSC model with inducible expression, Western blot (phospho-AKT) The Journal of pathology High 35342947
2022 ETV6-NCOA2 forms a transcriptional complex with ETV6 and histone acetyltransferase p300, leading to derepression of ETV6 target genes. Expression in nonthymic hematopoietic progenitors (mouse BM and human CD34+ cord blood) induces T/myeloid leukemia by activating a lymphoid program while failing to repress myeloid genes (CSF1, MEF2C); co-acquisition of activating NOTCH1 mutations is required for full leukemic transformation. Co-immunoprecipitation (ETV6-NCOA2/ETV6/p300 complex), ChIP, mouse BM transduction/transplantation model, human cord blood xenograft model, gene expression profiling Blood High 34624096
2023 Ncoa2 promotes CD8+ T cell activation and antitumor immunity by upregulating PGC-1α expression to enhance mitochondrial biogenesis and function. T-cell activation-induced CREB phosphorylation triggers Ncoa2 recruitment to PGC-1α enhancers. T cell-specific Ncoa2 knockout (Ncoa2fl/fl/CD4Cre) causes defective mitochondrial mass increase, impaired oxidative phosphorylation, reduced IFNγ, and failure to reject tumors. Forced PGC-1α expression rescues these defects. Conditional T cell-specific KO mice, ChIP (CREB-induced Ncoa2 enhancer recruitment), mitochondrial functional assays, adoptive transfer tumor rejection, PGC-1α rescue experiment Cancer immunology research High 37540802
2023 HEY1-NCOA2 expression in mouse embryonic superficial zone cells induces mesenchymal chondrosarcoma with biphasic morphology. HEY1-NCOA2 interacts with Runx2 (via NCOA2 C-terminal domains) and enhances chondrocyte differentiation gene programs; ChIP-seq shows frequent interaction between HEY1-NCOA2 binding peaks and active enhancers. Runx2 knockout delays tumor onset but induces aggressive small round cell growth. HDAC inhibitor panobinostat suppresses tumor growth by abrogating HEY1-NCOA2/Runx2 downstream gene expression. Mouse tumor model, ChIP-seq, co-immunoprecipitation (HEY1-NCOA2/Runx2), HDAC inhibitor treatment, gene expression analysis JCI insight High 37212282
2024 KAT6 (MOZ/MORF) enzymatic activity and the MOZ-TIF2 protein itself are necessary for indefinite proliferation of MOZ-TIF2 AML cells; pharmacological inhibition or targeted protein degradation of KAT6 activity abolishes this. MOZ-TIF2 directly regulates a small subset of developmental transcription factor genes, and transcription levels correlate with enrichment of histone H3 propionylation at lysine 23 (H3K23pr). Pharmacological KAT6 inhibition, targeted protein degradation (PROTAC), histone modification profiling (H3K23pr), ChIP, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 38889153

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. The EMBO journal 904 8670870
2004 MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer cell 532 15607963
1997 RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proceedings of the National Academy of Sciences of the United States of America 495 9238002
1998 The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. The EMBO journal 430 9430642
2002 SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 367 12507421
2011 Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes, chromosomes & cancer 245 22034177
1998 A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Blood 220 9558366
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
2013 Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma. Genes, chromosomes & cancer 184 23463663
1998 Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2). Molecular endocrinology (Baltimore, Md.) 177 9717843
2003 MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer cell 171 12676584
2000 Differential expression and regional distribution of steroid receptor coactivators SRC-1 and SRC-2 in brain and pituitary. Endocrinology 164 10830308
2003 Beta-catenin binds to the activation function 2 region of the androgen receptor and modulates the effects of the N-terminal domain and TIF2 on ligand-dependent transcription. Molecular and cellular biology 142 12588987
2001 Factor recruitment and TIF2/GRIP1 corepressor activity at a collagenase-3 response element that mediates regulation by phorbol esters and hormones. The EMBO journal 140 11689447
2008 Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science (New York, N.Y.) 137 19039140
1989 An essential yeast protein, encoded by duplicated genes TIF1 and TIF2 and homologous to the mammalian translation initiation factor eIF-4A, can suppress a mitochondrial missense mutation. Proceedings of the National Academy of Sciences of the United States of America 126 2648398
2012 Fusion of the AHRR and NCOA2 genes through a recurrent translocation t(5;8)(p15;q13) in soft tissue angiofibroma results in upregulation of aryl hydrocarbon receptor target genes. Genes, chromosomes & cancer 125 22337624
2000 Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2. EMBO reports 121 11265755
1998 Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2. Blood 116 9731070
2015 Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis. The Journal of clinical investigation 94 25664849
1998 Mechanistic principles in NR box-dependent interaction between nuclear hormone receptors and the coactivator TIF2. Molecular and cellular biology 88 9742117
2014 Androgen deprivation-induced NCoA2 promotes metastatic and castration-resistant prostate cancer. The Journal of clinical investigation 86 25295534
2010 PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nature medicine 82 20418886
2019 Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Distinct Entity Characterized by Recurrent NCOA2/3 Gene Fusions. The American journal of surgical pathology 78 30273195
2014 SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell reports 71 24529706
2008 ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations. Clinical cancer research : an official journal of the American Association for Cancer Research 67 18281529
2008 MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish. British journal of haematology 65 18729850
1999 Oligospermic infertility associated with an androgen receptor mutation that disrupts interdomain and coactivator (TIF2) interactions. The Journal of clinical investigation 61 10359561
2010 The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. Cell metabolism 60 21035760
2012 A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer. Proceedings of the National Academy of Sciences of the United States of America 59 22556267
2004 Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction. Proceedings of the National Academy of Sciences of the United States of America 58 15070739
2002 The nuclear receptor coactivators p300/CBP/cointegrator-associated protein (p/CIP) and transcription intermediary factor 2 (TIF2) differentially regulate PKA-stimulated transcriptional activity of steroidogenic factor 1. Molecular endocrinology (Baltimore, Md.) 56 11923473
2009 Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2. Molecular cancer therapeutics 55 19240160
2013 Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. The Journal of biological chemistry 52 23558686
2005 Interaction of beta-catenin and TIF2/GRIP1 in transcriptional activation by the androgen receptor. The Journal of biological chemistry 48 16141201
2018 Novel MEIS1-NCOA2 Gene Fusions Define a Distinct Primitive Spindle Cell Sarcoma of the Kidney. The American journal of surgical pathology 46 30179902
2005 MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function. Molecular and cellular biology 46 15657427
2021 Recurrent MEIS1-NCOA2/1 fusions in a subset of low-grade spindle cell sarcomas frequently involving the genitourinary and gynecologic tracts. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 45 33574497
2015 Metformin inhibits hepatocellular glucose, lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2 (SRC-2). Scientific reports 43 26548416
2014 Trypanosoma brucei TIF2 suppresses VSG switching by maintaining subtelomere integrity. Cell research 42 24810301
2020 Uterine Tumor Resembling Ovarian Sex Cord Stromal Tumor (UTROSCT): A Series of 3 Cases With Extensive Rhabdoid Differentiation, Malignant Behavior, and ESR1-NCOA2 Fusions. The American journal of surgical pathology 41 32675660
2011 Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis. The Journal of cell biology 40 21220509
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
2012 Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations. The Journal of biological chemistry 38 23132854
2012 Detection of HEY1-NCOA2 fusion by fluorescence in-situ hybridization in formalin-fixed paraffin-embedded tissues as a possible diagnostic tool for mesenchymal chondrosarcoma. Pathology international 37 23252872
2002 Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: evidence for haploinsufficiency. Endocrinology 37 11897715
2000 Human androgen receptor mutation disrupts ternary interactions between ligand, receptor domains, and the coactivator TIF2 (transcription intermediary factor 2). Molecular endocrinology (Baltimore, Md.) 36 10935543
2014 Chromosome aberrations and HEY1-NCOA2 fusion gene in a mesenchymal chondrosarcoma. Oncology reports 35 24839999
2006 STAMP, a novel predicted factor assisting TIF2 actions in glucocorticoid receptor-mediated induction and repression. Molecular and cellular biology 35 17116691
2017 RNA-sequencing identifies novel GREB1-NCOA2 fusion gene in a uterine sarcoma with the chromosomal translocation t(2;8)(p25;q13). Genes, chromosomes & cancer 34 29218853
2013 Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion. International journal of hematology 33 24258712
2014 Diagnostic utility of NCOA2 fluorescence in situ hybridization and Stat6 immunohistochemistry staining for soft tissue angiofibroma and morphologically similar fibrovascular tumors. Human pathology 31 24856853
2009 cAMP enhances estrogen-related receptor alpha (ERRalpha) transcriptional activity at the SP-A promoter by increasing its interaction with protein kinase A and steroid receptor coactivator 2 (SRC-2). Molecular endocrinology (Baltimore, Md.) 31 19264843
2002 PIAS3 (protein inhibitor of activated STAT-3) modulates the transcriptional activation mediated by the nuclear receptor coactivator TIF2. FEBS letters 30 12208521
2015 Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer. Oncogene 29 25823027
2016 Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma. Oncology reports 28 27633981
2007 Amino-terminal domain of TIF2 is involved in competing for corepressor binding to glucocorticoid and progesterone receptors. Biochemistry 28 17571860
2018 Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells. Blood 27 29371181
2002 TIF2 mediates the synergy between RARalpha 1 activation functions AF-1 and AF-2. The Journal of biological chemistry 27 12149266
2018 Indeterminate Dendritic Cell Tumor: A Report of Two New Cases Lacking the ETV3-NCOA2 Translocation and a Literature Review. The American Journal of dermatopathology 25 29877893
2016 Trypanosoma brucei TIF2 and TRF Suppress VSG Switching Using Overlapping and Independent Mechanisms. PloS one 25 27258069
2013 PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells. Oncogene 25 24213582
2006 Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 17135362
2004 The genes of the coactivator TIF2 and the corepressor SMRT are primary 1alpha,25(OH)2D3 targets. The Journal of steroid biochemistry and molecular biology 24 15225781
2022 ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells. Blood 23 34624096
2006 MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta2 promoter: differential effects of MOZ fusion proteins on CBP- and MOZ-dependent activators. The Journal of biological chemistry 23 16613851
2022 Genomic profiling identifies genes and pathways dysregulated by HEY1-NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis. The Journal of pathology 22 35342947
2022 Mesenchymal chondrosarcoma of the head and neck with HEY1::NCOA2 fusion: A clinicopathologic and molecular study of 13 cases with emphasis on diagnostic pitfalls. Genes, chromosomes & cancer 22 35672279
2021 PFKFB4 promotes lung adenocarcinoma progression via phosphorylating and activating transcriptional coactivator SRC-2. BMC pulmonary medicine 21 33593309
2016 Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology. Journal of biological rhythms 21 27432117
2012 SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart. PloS one 21 23300926
2015 NcoA2-Dependent Inhibition of HIF-1α Activation Is Regulated via AhR. Toxicological sciences : an official journal of the Society of Toxicology 20 26350169
2004 Nuclear structure-associated TIF2 recruits glucocorticoid receptor and its target DNA. Biochemical and biophysical research communications 20 15207724
2023 Ncoa2 Promotes CD8+ T cell-Mediated Antitumor Immunity by Stimulating T-cell Activation via Upregulation of PGC-1α Critical for Mitochondrial Function. Cancer immunology research 19 37540802
2019 NCOA2 promotes lytic reactivation of Kaposi's sarcoma-associated herpesvirus by enhancing the expression of the master switch protein RTA. PLoS pathogens 19 31751430
2006 Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TIF2. Molecular and cellular endocrinology 19 16469430
2003 A further case of acute myelomonocytic leukemia with inv(8) chromosomal rearrangement and MOZ-NCOA2 gene fusion. International journal of molecular medicine 19 12964013
2021 Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR). Journal of molecular biology 18 33647291
2017 SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer. PLoS genetics 18 28273073
1998 Cloning and characterization of a transforming growth factor beta 1-induced anti-apoptotic adhesion protein TIF2. Biochemical and biophysical research communications 18 9705873
2015 Polymorphisms in TOX and NCOA2 genes and their associations with reproductive traits in cattle. Reproduction, fertility, and development 17 25482955
2023 HEY1-NCOA2 expression modulates chondrogenic differentiation and induces mesenchymal chondrosarcoma in mice. JCI insight 16 37212282
2018 Retinoid signaling controlled by SRC-2 in decidualization revealed by transcriptomics. Reproduction (Cambridge, England) 15 30325183
2014 Angiofibroma of soft tissue with fibrohistiocytic features and intratumor genetic heterogeneity of NCOA2 gene rearrangement revealed by chromogenic in situ hybridization: a case report. Pathology international 15 24888778
2023 Uterine MEIS1::NCOA2 Fusion Sarcoma With Lung Metastasis: A Case Report and Review of the Literature. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 14 37043646
2016 NCOA2 is a candidate target gene of 8q gain associated with clinically aggressive prostate cancer. Genes, chromosomes & cancer 14 26799514
2023 VGLL2-NCOA2 leverages developmental programs for pediatric sarcomagenesis. Cell reports 13 36656711
2021 Spindle Cell Sarcoma of the Uterine Corpus With Adipose Metaplasia: Expanding the Morphologic Spectrum of Neoplasms With MEIS1-NCOA2 Gene Fusion. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 13 34166279
2013 Expression and characterization of androgen receptor coregulators, SRC-2 and HBO1, during human testis ontogenesis and in androgen signaling deficient patients. Molecular and cellular endocrinology 13 23707616
2024 A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes. Proceedings of the National Academy of Sciences of the United States of America 12 38889153
2023 Aggressive High-grade Uterine Sarcoma Harboring MEIS1-NCOA2 Fusion and Amplification of Multiple 12q13-15 Genes: A Case Report With Morphologic, Immunohistochemical, and Molecular Analysis. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 12 36811835
2016 Expression of the MOZ-TIF2 oncoprotein in mice represses senescence. Experimental hematology 12 26854485
2015 Association of NCOA2 gene polymorphisms with obesity and dyslipidemia in the Chinese Han population. International journal of clinical and experimental pathology 12 26261634
2014 Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: A paediatric case report and review of the literature. Oncology letters 12 25202377
2009 Estrogen signaling in colorectal carcinoma microenvironment: expression of ERbeta1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression. Virchows Archiv : an international journal of pathology 12 19277704
2002 Coactivation of an endogenous progesterone receptor by TIF2 in COS-7 cells. Biochemical and biophysical research communications 12 12150973
2023 Intraosseous Spindle Cell Rhabdomyosarcoma with MEIS1::NCOA2 Fusion - Case Report with Substantial Clinical Follow-up and Review of the Literature. Cancer investigation 11 37668330
2020 SRC-2 Coactivator: a role in human metabolic evolution and disease. Molecular medicine (Cambridge, Mass.) 11 32410572
2015 SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis. Proceedings of the National Academy of Sciences of the United States of America 11 26487680
2012 Separate regions of glucocorticoid receptor, coactivator TIF2, and comodulator STAMP modify different parameters of glucocorticoid-mediated gene induction. Molecular and cellular endocrinology 11 22342989

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