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Showing TADA3 — ADA3 is a alias.

TADA3

Transcriptional adapter 3 · UniProt O75528

Length
432 aa
Mass
48.9 kDa
Annotated
2026-06-10
38 papers in source corpus 30 papers cited in narrative 30 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

TADA3/ADA3 is an evolutionarily conserved, non-enzymatic scaffold subunit of GCN5/PCAF-containing histone acetyltransferase (HAT) complexes that links transcriptional activators to chromatin acetylation and is required for cell proliferation, genome stability, and chromosome segregation (PMID:7862114, PMID:11773077, PMID:22736770). In yeast it was first defined genetically as a member of the ADA pathway acting together with ADA2 at activator-regulated promoters (PMID:8413201, PMID:8262068), and reconstitution established that ADA2, ADA3, and GCN5 form a heterotrimeric catalytic core—with ADA2 as the linchpin—that is necessary and sufficient for nucleosomal HAT activity and expanded lysine specificity, ADA3 specifically facilitating nucleosomal acetylation (PMID:7862114, PMID:11773077). Within these complexes ADA3 serves as a coactivator that bridges sequence-specific factors to acetyltransferase activity: it directly binds nuclear hormone receptors ERα/β and RARα through its LxxLL motifs in a hormone-dependent manner, occupies native target promoters, and is required for receptor-driven gene expression and estrogen-dependent proliferation (PMID:15496419, PMID:18089809, PMID:20413580); it potentiates β-catenin/Wnt target gene activation by promoting β-catenin acetylation (PMID:18059173); and it acts as a direct p53 coactivator, binding p53 (an interaction enhanced by DNA-damage-induced p53 phosphorylation) and promoting p300/CBP-mediated p53 acetylation to stabilize p53 and induce target genes and senescence (PMID:11707411, PMID:17272277, PMID:17452980). ADA3 is itself acetylated in a cell-cycle-dependent manner by GCN5, PCAF, and p300 and deacetylated by SIRT1, and this acetylation—regulated by an RTK–AKT–p300 axis that also controls ADA3 stability—is required for global histone acetylation and proliferation (PMID:27402865, PMID:28759294). Beyond transcription, ADA3 localizes to centromeres via direct interaction with CENP-B to control CENP-B loading and chromosome segregation (PMID:26429915), is required for DNA repair and genomic stability (PMID:23095635), and acts with PCAF upstream of PACS2 in granzyme B-mediated Bid processing during apoptosis (PMID:24464226). High-risk HPV E6 selectively binds ADA3 and targets it for E6AP-mediated, SUMOylation-potentiated proteasomal degradation, thereby inactivating its p53- and p14ARF-dependent tumor-suppressive functions independently of direct p53 degradation (PMID:12138191, PMID:18256148, PMID:24795430).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 Medium

    Established ADA3/NGG1 as a genetic component of the activator-response and glucose-repression machinery, placing it functionally alongside ADA2 rather than as an independent factor.

    Evidence Genetic epistasis, double-mutant analysis, in vitro transcription and reporter assays in yeast

    PMID:8262068 PMID:8413201

    Open questions at the time
    • No biochemical mechanism or physical complex defined
    • Molecular activity of ADA3 itself unknown
  2. 1995 High

    Defined the physical basis of the ADA pathway by reconstituting an ADA2-ADA3-GCN5 heterotrimer and mapping ADA3 domains, answering how the genetic partners assemble into a complex.

    Evidence In vitro reconstitution and domain-deletion mapping with in vivo activation assays

    PMID:7862114

    Open questions at the time
    • Catalytic consequence of trimer assembly not yet tested on nucleosomes
    • Role of N- vs C-terminal domains in activation only inferred
  3. 1997 High

    Showed ADA3 and ADA2 are mutually stabilizing, near-stoichiometric partners residing in multiple higher-order complexes and contacting TBP, refining the architecture of native ADA/GCN5 complexes.

    Evidence Reciprocal co-IP with quantification, ion-exchange and gel-filtration chromatography in yeast extracts

    PMID:9038164 PMID:9154821

    Open questions at the time
    • Functional roles of distinct complex sizes not resolved
    • ADA1/ADA5 functional class distinction left mechanistically open
  4. 2001 High

    Demonstrated the ADA2-ADA3-GCN5 core is necessary and sufficient for nucleosomal HAT activity and lysine specificity, assigning ADA3 a specific role in nucleosomal acetylation and expanded substrate range.

    Evidence In vitro reconstituted HAT assays on nucleosome substrates and yeast extract assays

    PMID:11773077

    Open questions at the time
    • Structural basis of ADA3-dependent specificity not determined
    • Whether human core behaves identically not yet tested at this stage
  5. 2001 High

    Extended ADA3 function to a human tumor-suppressor pathway by showing it binds p53 (enhanced after DNA damage) and is required for full p53 transcriptional activity and apoptosis.

    Evidence Yeast p53 dissociator assay, co-IP in human cells, transcription and apoptosis assays

    PMID:11707411

    Open questions at the time
    • Acetylation-based mechanism of p53 activation not yet defined
    • Which HAT complex mediates the effect not specified
  6. 2002 High

    Identified ADA3 as a selective high-risk HPV E6 target whose degradation inactivates p53 independently of p53 degradation, defining a distinct viral oncogenic mechanism.

    Evidence Co-IP, degradation assays with E6 mutants, transcriptional and cell-cycle assays

    PMID:12138191

    Open questions at the time
    • Ubiquitin ligase mediating degradation not yet identified
    • Whether other ADA3 functions are also disrupted not addressed
  7. 2002 Medium

    Established ADA3 as a nuclear-receptor coactivator by showing direct RXRα binding and promoter occupancy, while the mouse TFTC study showed nuclear-receptor contact can occur through other subunits, framing how receptor coupling is achieved.

    Evidence In vitro binding, co-IP, ChIP at native p21 promoter; TFTC complex co-IP with ERα

    PMID:12034840 PMID:12235159

    Open questions at the time
    • Direct vs complex-mediated receptor contact appeared species/context dependent
    • LxxLL-motif usage not yet functionally tested
  8. 2004 High

    Confirmed ADA3 as a direct ERα/ERβ coactivator required for endogenous estrogen target gene expression, linking it to estrogen-responsive transcription.

    Evidence Direct binding, ChIP at native pS2 promoter, RNAi knockdown, RT-PCR of multiple targets

    PMID:15496419

    Open questions at the time
    • HAT recruitment role not yet demonstrated
    • Contribution to proliferation not yet shown
  9. 2007 High

    Defined the molecular mechanism of ADA3-mediated p53 activation—promotion of p300/CBP-dependent p53 acetylation and stabilization—and separated p53-binding from p300-binding functions required for p14ARF-induced senescence.

    Evidence shRNA/siRNA knockdown, inducible overexpression, p53 acetylation-site and ADA3 N-terminal-domain mutagenesis, co-IP

    PMID:17272277 PMID:17452980

    Open questions at the time
    • Stoichiometry of ADA3 in p300 complexes not resolved
    • Direct enzymatic contribution of ADA3 (non-catalytic) to acetylation not structurally explained
  10. 2007 High

    Demonstrated ADA3 is required for ligand-dependent recruitment of p300, PCAF, and GCN5 to ER target promoters and for estrogen-dependent breast cancer proliferation, linking its coactivator role to a proliferative oncogenic output.

    Evidence Glycerol gradient cosedimentation, co-IP, ChIP, shRNA knockdown, 2D/3D proliferation assays

    PMID:18089809

    Open questions at the time
    • Whether ADA3 acts as scaffold for HAT delivery vs activator bridging not dissected
    • Generality beyond ER promoters not tested here
  11. 2007 Medium

    Broadened ADA3 coactivator function to Wnt signaling by showing it (with ADA2a) binds β-catenin, occupies the c-Myc enhancer, and promotes β-catenin acetylation and target gene activation.

    Evidence Co-IP with domain mapping, ChIP, RNAi, reporter assays

    PMID:18059173

    Open questions at the time
    • Single-lab finding without reciprocal in vivo validation
    • Whether β-catenin is a direct ADA3-complex acetylation substrate not proven
  12. 2007 High

    Provided conserved in vivo loss-of-function evidence that the ADA3 ortholog is required for specific GCN5-dependent histone marks (H3K9/K14, H4K12) and for organismal viability and oogenesis.

    Evidence Drosophila genetic mutants, histone-modification immunostaining, genetic interaction analysis

    PMID:17967867

    Open questions at the time
    • Mechanism restricting specificity to particular lysines unexplained
    • Direct vs indirect effect on H3S10 phosphorylation unresolved
  13. 2008 Medium

    Showed ADA3 degradation alone is sufficient for HPV E6-driven immortalization and inactivation of the p14ARF-p53 pathway, and identified ANCO-1/2 as ADA3-interacting regulators that modulate its coactivator activity.

    Evidence E6 mutant immortalization assays; co-IP, domain mapping, co-localization, reporter assays for ANCO proteins

    PMID:18256148 PMID:18377363

    Open questions at the time
    • ANCO regulatory mechanism single-lab and not validated in vivo
    • How ADA3 loss bypasses p53 levels mechanistically not fully resolved
  14. 2009 Medium

    Identified E6AP as the ubiquitin ligase required for HPV16 E6-induced ADA3 degradation and linked ADA3 restoration to reduced proliferation and increased apoptosis in cervical carcinoma cells.

    Evidence siRNA knockdown of E6/E6AP, protein expression, proliferation and apoptosis assays

    PMID:19194825

    Open questions at the time
    • Direct ubiquitination of ADA3 by E6AP not biochemically reconstituted here
    • Single-lab phenotypic readouts
  15. 2010 High

    Established the direct, LxxLL-motif-dependent mechanism by which ADA3 engages RARα, confirmed by reciprocal mutagenesis of both the motifs and the receptor coactivator pocket.

    Evidence Co-IP, LxxLL and coactivator-pocket mutagenesis, ChIP at native promoter, siRNA, structural modeling

    PMID:20413580

    Open questions at the time
    • Whether LxxLL usage is identical across all receptors not fully generalized
    • Crystallographic structure of the interaction not obtained
  16. 2012 High

    Defined the essential cellular requirement for ADA3 in mammals: embryonic lethality, proliferation and cell-cycle defects via c-Myc/p27 regulation, mitotic defects, global histone acetylation changes, and a requirement for DNA repair and genomic stability.

    Evidence Germline and conditional knockout mice, MEF deletion with human ADA3 rescue, cell-cycle, microarray, histone and DNA-damage marker analyses, cytogenetics, comet assay

    PMID:22736770 PMID:23095635

    Open questions at the time
    • Direct vs indirect contribution to specific repair pathways not dissected
    • Link between histone acetylation defect and repair phenotype not mechanistically resolved
  17. 2013 Medium

    Expanded the ADA3 interactome to AATF and the phosphatase regulatory subunits PPP1R7 and PPP2R5D through an ADA2-independent N-terminal region, hinting at links to apoptosis regulation and phosphatase activity.

    Evidence Yeast two-hybrid screen, co-IP, fluorescence microscopy, reporter assays

    PMID:23167988

    Open questions at the time
    • Functional consequences of phosphatase-subunit binding untested
    • Single-lab interactions without reciprocal in vivo validation
  18. 2014 High

    Placed ADA3 (with PCAF) upstream of PACS2 in the granzyme B apoptosis pathway controlling Bid cleavage, and showed HPV E6-driven ADA3 turnover is potentiated by prior SUMOylation, ordering the degradation mechanism.

    Evidence shRNA/siRNA screens, cytochrome c and Bid cleavage assays, PACS2 epistasis; ubiquitination/SUMOylation assays with Ubc9 depletion

    PMID:24464226 PMID:24795430

    Open questions at the time
    • How ADA3/PCAF transcriptionally controls PACS2 not detailed
    • SUMOylation sites and ubiquitin-SUMO crosstalk single-lab
  19. 2015 High

    Revealed a non-transcriptional centromeric role: ADA3 binds alpha-satellite DNA and directly interacts with CENP-B via its N-terminus to promote CENP-B loading and support proliferation through chromosome segregation control.

    Evidence Proximity ligation, immunofluorescence, deletion mapping, ChIP on alpha-satellite DNA, CENP-B loading and proliferation rescue with binding-deficient mutant

    PMID:26429915

    Open questions at the time
    • Whether HAT activity is involved at centromeres not addressed
    • Relationship to the mitotic defects seen in ADA3-null MEFs not directly linked
  20. 2016 High

    Established that ADA3 is itself regulated by cell-cycle-dependent acetylation (by GCN5, PCAF, p300; reversed by SIRT1) that is functionally required for global histone acetylation and proliferation, and that ADA3-driven c-MYC underlies its proliferative role.

    Evidence Mass spectrometry, site-directed mutagenesis, HAT assays, rescue of ADA3-null MEFs with acetylation-defective mutants; overexpression with molecular readouts

    PMID:27402865 PMID:27852327

    Open questions at the time
    • How acetylation alters ADA3 function at the structural level unknown
    • Interplay of individual acetylation sites not fully dissected
  21. 2017 Medium

    Connected upstream growth-factor signaling to ADA3 regulation, defining an RTK/EGFR-HER2–AKT–p300 axis that acetylates and stabilizes ADA3, with acetylation competing against ubiquitination on shared lysines.

    Evidence Lapatinib treatment, p300 phosphorylation and ADA3 stability assays, K→R mutagenesis, proteasome inhibition

    PMID:28759294

    Open questions at the time
    • Direct shared-lysine competition not structurally proven
    • Single-lab pharmacological pathway dissection

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADA3 mechanistically integrates its distinct functions—HAT scaffolding, coactivator bridging, centromeric CENP-B loading, and DNA repair—and whether a high-resolution structure explains its non-catalytic specificity and acetylation-dependent switching remains unresolved.
  • No high-resolution structure of human ADA2-ADA3-GCN5 core
  • Unified model linking transcriptional and centromeric/repair roles absent
  • Direct substrate scope of ADA3-containing complexes in vivo incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0003677 DNA binding 1
Localization
GO:0005654 nucleoplasm 3 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
ADA2/TADA2ACENP-BESR1GCN5P300P53PCAFRARA
Complex memberships
ADA2-ADA3-GCN5 corePCAF complexSAGA/ADA HAT complexTFTC

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 ADA3 (NGG1) was identified as a yeast gene whose mutations prevent toxicity of GAL4-VP16; double disruption of ada2 and ada3 showed no additive growth defect, placing ADA3 in the same pathway as ADA2. Selection of transcription initiation sites in vitro was altered in ada3 mutants, suggesting a role in the response to acidic activators. Genetic epistasis (double mutant analysis), in vitro transcription initiation assay Molecular and cellular biology Medium 8413201
1993 NGG1 (ADA3) was identified as required for glucose repression of GAL4p-activated genes; its activity was GAL4-dependent and promoter analysis showed a correlation between the number of GAL4p binding sites and NGG1p activity, establishing a functional role in repression at GAL4-regulated promoters. Genetic screen, promoter deletion analysis, reporter assays in yeast The EMBO journal Medium 8262068
1995 ADA2, ADA3, and GCN5 form a heterotrimeric complex in vitro, with ADA2 serving as the linchpin holding ADA3 and GCN5 together. The C-terminal domain of ADA3 is sufficient for complex formation, while the N-terminal domain mediates interaction between activation domains and the ADA complex. In vitro reconstitution, domain deletion analysis, in vivo activation assays Molecular and cellular biology High 7862114
1996 NGG1p/ADA3p requires residues 274-373 (including an amphipathic alpha-helix rich in Phe residues) for glucose repression. Single and double disruptions of ngg1 and ada2 had comparable effects on glucose repression, confirming they act in the same complex. An ADA2p-interaction site was mapped to residues 308-373 of NGG1p. Deletion mutagenesis, genetic epistasis, in vivo reporter assays The Journal of biological chemistry Medium 8621592
1997 NGG1p/ADA3p and ADA2p are co-immunoprecipitated from yeast whole-cell extracts (less than 2% of ADA2p was not associated with NGG1p), and each protein's stability depends on the other. NGG1p-containing complexes of approximately 200 kDa, 900 kDa, and >2 MDa were resolved, and TBP co-immunoprecipitated with NGG1p in a manner requiring NGG1p residues 274-307. Co-immunoprecipitation, ion-exchange chromatography, gel filtration The Journal of biological chemistry High 9038164
1997 ADA1 interacts with ADA3 and other ADA complex members as shown by partial purification and immunoprecipitation, and the ADA/GCN5 complex has an estimated molecular mass of approximately 2 MDa. ADA1 and ADA5 mutations produce more severe defects than ada2/ada3/gcn5 mutations, suggesting two functional classes within the complex. Partial complex purification, co-immunoprecipitation, genetic phenotypic analysis Molecular and cellular biology Medium 9154821
2001 Yeast Ada2, Ada3, and Gcn5 form the catalytic core of ADA and SAGA HAT complexes; this trimeric core is necessary and sufficient for nucleosomal HAT activity and lysine specificity in vitro. Ada3 is necessary for Gcn5-dependent nucleosomal HAT activity in yeast extracts; Ada2 potentiates Gcn5 catalytic activity, while Ada3 facilitates nucleosomal acetylation and expanded lysine specificity. In vitro reconstitution of HAT activity with nucleosome substrates, yeast extract HAT assays The Journal of biological chemistry High 11773077
2001 hADA3 physically interacts with p53 in human cells; this interaction is enhanced after DNA damage due to phosphorylation of the p53 N-terminus. hADA3 is required for full p53 transcriptional activity and p53-mediated apoptosis, and was identified as a component of histone acetyltransferase complexes. Yeast p53 dissociator assay, co-immunoprecipitation in human cells, functional transcription and apoptosis assays The EMBO journal High 11707411
2002 hADA3 binds selectively to high-risk HPV E6 proteins (not low-risk) and is targeted for E6-induced degradation. HPV E6 mutants that cannot degrade p53 but can interact with hADA3 abrogate p53-mediated transactivation and G1 arrest after DNA damage, revealing a p53-degradation-independent mechanism of p53 inactivation via hADA3. Co-immunoprecipitation, protein degradation assays, transcriptional reporter assays, cell cycle analysis Molecular and cellular biology High 12138191
2002 hADA3 directly binds RXRalpha in vitro and in vivo, and is part of activator complexes bound to native RXR response elements within the p21 promoter as shown by chromatin immunoprecipitation. hADA3 enhances RXRalpha-mediated transactivation of retinoid target genes, and HPV E6 inhibits this RXRalpha-mediated transactivation by targeting hADA3. In vitro binding assay, co-immunoprecipitation, chromatin immunoprecipitation, transcriptional reporter assay The Journal of biological chemistry High 12235159
2002 Mouse mADA3-containing TFTC (TBP-free-TAF-containing) complex interacts with ERalpha in a ligand-independent manner; mADA3 itself does not directly interact with nuclear receptors despite containing two LxxLL NR boxes, indicating other complex subunits mediate the interaction. Co-immunoprecipitation, cloning and characterization of mouse ADA3 Nucleic acids research Medium 12034840
2004 hADA3 directly interacts with ERalpha and ERbeta; hADA3 is a component of activator complexes bound to the native ER response element in the pS2 promoter (shown by ChIP); RNA interference-mediated knockdown of endogenous hADA3 inhibited ER-mediated transactivation and estrogen-induced expression of pS2, cathepsin D, and progesterone receptor. Co-immunoprecipitation, chromatin immunoprecipitation, RNA interference, transcriptional reporter assay, RT-PCR The Journal of biological chemistry High 15496419
2007 hAda3 stabilizes p53 protein by promoting its acetylation at p300/CBP sites; hAda3-dependent acetylation is required for increased p53 stability and target gene induction. Endogenous hAda3 is essential for DNA damage-induced acetylation and stabilization of p53, placing hAda3 as a component of p300/CBP-containing coactivator complexes that mediate p53 acetylation. shRNA knockdown, inducible overexpression, site-directed mutagenesis of p53 acetylation sites, co-immunoprecipitation The Journal of biological chemistry High 17272277
2007 p14ARF-induced senescence requires hAda3; expression of the N-terminal domain of hAda3 (which binds p53 but not p300) blocked p14ARF-induced p53 acetylation and senescence. hAda3 overexpression increased p300-mediated p53 acetylation, and siRNA knockdown decreased p53 acetylation and p21cip1 accumulation in response to p14ARF. Domain expression (N-terminal fragment), siRNA knockdown, HPV16 E6 mutant Y54D selective degradation, p53 acetylation assays Oncogene High 17452980
2007 Ada3, ERalpha, and three HATs (p300, PCAF, and Gcn5) are present in a complex demonstrated by glycerol gradient cosedimentation and immunoprecipitation. shRNA-mediated knockdown of Ada3 in ER-positive breast cancer cells significantly reduced ligand-dependent recruitment of p300, PCAF, and Gcn5 to the ER-responsive pS2 promoter, and Ada3 is critical for estrogen-dependent proliferation. Glycerol gradient cosedimentation, co-immunoprecipitation, chromatin immunoprecipitation, shRNA knockdown, 2D/3D proliferation assays Cancer research High 18089809
2007 hADA2a and hADA3 physically interact with beta-catenin through its Armadillo repeats 6-12 and C-terminal transactivation domain; both proteins reside with beta-catenin at the c-Myc enhancer. RNAi-mediated reduction of hADA2a and hADA3 results in reduced beta-catenin acetylation, reduced reporter activity, and reduced activation of endogenous Wnt target genes. Co-immunoprecipitation, chromatin immunoprecipitation, RNA interference, transcriptional reporter assays, domain mapping Cancer biology & therapy Medium 18059173
2007 Drosophila dADA3 localizes to chromosomes and its levels are significantly reduced in dGcn5 and dAda2a (but not dAda2b) mutant backgrounds. dAda3 mutants show reduced acetylation specifically at histone H3 K9 and K14 (not K18) and H4 K12 (not K5, K8, K16), and reduced H3 S10 phosphorylation also seen in dGcn5 mutants. dADA3 is required for oogenesis and somatic cell viability. Genetic mutant analysis, immunostaining for histone modifications, localization studies, genetic interaction Molecular and cellular biology High 17967867
2008 ANCO-1 and ANCO-2 interact with ADA3; the interaction occurs between the conserved C-terminal domain of ANCO-1 and the N-terminal transactivation domain of ADA3. ANCO-1 colocalizes with ADA3, ADA2alpha/beta, and PCAF at nuclear dots in vivo. ANCO-1 and ANCO-2 repress ADA3-mediated transcriptional co-activation on nuclear receptors, while ANCO-1 stimulates p53-mediated transactivation. Co-immunoprecipitation, domain mapping, immunofluorescence co-localization, transcriptional reporter assay The Biochemical journal Medium 18377363
2008 HPV16 E6 mutants that degrade hAda3 but not p53 abrogate p14ARF-induced growth arrest and efficiently immortalize mammary epithelial cells despite normal p53 levels, establishing that hAda3 degradation (not only p53 degradation) is sufficient for inactivation of the p14ARF-p53 pathway. HPV16 E6 mutant analysis, protein degradation assays, cell proliferation/immortalization assays Journal of virology Medium 18256148
2009 HPV16 E6-induced degradation of hADA3 in cervical carcinoma cells is E6AP-dependent; siRNA knockdown of E6 or E6AP increased hADA3 protein levels, decreased cellular proliferation, and increased apoptotic rate. siRNA knockdown, protein expression analysis, proliferation and apoptosis assays Cancer investigation Medium 19194825
2010 hADA3 interacts directly with RARalpha in a hormone-dependent manner through its LxxLL motifs engaging the receptor coactivator pocket; loss- and gain-of-function mutations in LxxLL motifs and the receptor coactivator pocket confirmed this mechanism. hADA3 associates with RARalpha target gene promoters in a hormone-dependent manner, and ADA3 knockdown impairs RARbeta2 expression. Co-immunoprecipitation, site-directed mutagenesis (LxxLL motifs and receptor coactivator pocket), chromatin immunoprecipitation, siRNA knockdown, structural modeling Nucleic acids research High 20413580
2012 Germline deletion of Ada3 in mouse is embryonic lethal; conditional deletion in MEFs causes severe proliferation defect, G1-to-S delay due to accumulation of CDK inhibitor p27 (an indirect effect of Ada3-regulated c-Myc transcription), mitotic defects, and drastic changes in global histone acetylation. Germline and conditional knockout mouse, adenovirus-Cre deletion of Ada3(FL/FL) MEFs, rescue by human Ada3 expression, cell cycle analysis, microarray, histone modification analysis The Journal of biological chemistry High 22736770
2012 Ada3 deletion leads to increased markers of DNA damage (pATM, gammaH2AX, p53BP1, pRAD51) in untreated cells and a significant delay in disappearance of DNA damage foci after ionizing radiation. Ada3-null cells show enhanced chromosomal aberrations (breaks, fragments, deletions, translocations), establishing Ada3 as required for the DNA repair process and genomic stability. Conditional Ada3 knockout (adenovirus-Cre in Ada3(fl/fl) MEFs), immunofluorescence for DNA damage markers, chromosomal aberration analysis, comet assay Cell cycle High 23095635
2013 Three novel hADA3-interacting partners were identified by yeast two-hybrid: AATF (apoptosis-antagonizing transcription factor), PPP1R7 (PP1 regulatory subunit), and PPP2R5D (PP2A regulatory subunit). The C-terminal ADA2-interacting domain of hADA3 was not required for these interactions. Co-localization and co-immunoprecipitation in human cells confirmed the interactions. Yeast two-hybrid screen, co-immunoprecipitation, fluorescence microscopy, transcriptional reporter assay The Biochemical journal Medium 23167988
2014 PCAF and ADA3 regulate granzyme B-mediated Bid cleavage upstream of mitochondrial membrane permeabilization; knockdown of PCAF or ADA3 reduced PACS2 expression, and PACS2 knockdown phenocopied the PCAF/ADA3 knockdown effect on Bid processing and cytochrome c release, placing ADA3-PCAF upstream of PACS2 in the granzyme B apoptosis pathway. shRNA screen, siRNA knockdown, cytochrome c release assay, Bid cleavage assay, genetic epistasis by PACS2 knockdown Cell death and differentiation High 24464226
2014 HPV16 E6 targets hADA3 for ubiquitin-mediated degradation via E6AP ubiquitin ligase; hADA3 undergoes SUMOylation that is accelerated in the presence of HPV16E6 and makes hADA3 unstable. Depletion of Ubc9 (SUMO E2 enzyme) prevented rapid hADA3 degradation, establishing that SUMOylation precedes and promotes E6-mediated ubiquitination of hADA3. Co-immunoprecipitation, ubiquitination assay, SUMOylation assay, Ubc9 depletion, protein stability assays Carcinogenesis Medium 24795430
2015 ADA3 associates with the higher-order repeat region of alpha-satellite DNA on human X chromosome centromeres, and directly interacts with centromere protein CENP-B through its N-terminus (shown by proximity ligation assay, immunofluorescence, and deletional analysis). Knockdown of ADA3 decreased CENP-B loading onto centromeres, and a CENP-B binding-deficient ADA3 mutant failed to rescue cell proliferation in Ada3-deleted MEFs. Proximity ligation assay, immunofluorescence, deletion mutagenesis, ChIP on alpha-satellite DNA, CENP-B loading assay, proliferation rescue assay The Journal of biological chemistry High 26429915
2016 ADA3 is acetylated in a cell cycle-dependent manner by GCN5, PCAF, and p300; SIRT1 is identified as a deacetylase that opposes this acetylation. Mass spectrometry and site-directed mutagenesis identified major acetylation sites. Acetylation-defective ADA3 mutants could interact with HATs but failed to restore global or locus-specific histone acetylation or cell proliferation in Ada3-deleted MEFs, establishing that ADA3 acetylation is functionally required. Mass spectrometry, site-directed mutagenesis, co-immunoprecipitation, HAT activity assays, rescue of Ada3-deleted MEFs Molecular and cellular biology High 27402865
2017 AKT activation downstream of EGFR/HER2 promotes phosphorylation of p300, which in turn promotes acetylation of ADA3. Lapatinib-mediated inhibition of HER1/HER2 reduced phospho-AKT, p300 phosphorylation, and ADA3 protein levels in a proteasome-dependent manner. An ADA3 K→R acetylation-site mutant showed increased half-life, consistent with competing acetylation and ubiquitination on shared lysines, establishing an RTK-AKT-p300-ADA3 signaling axis. Kinase inhibitor treatment (lapatinib), p300 phosphorylation assay, ADA3 stability assays, site-directed mutagenesis (K→R), proteasome inhibitor Cell cycle Medium 28759294
2016 ADA3 overexpression in mammary epithelial cells and ER+ breast cancer cells enhanced cell proliferation associated with increased cyclin B, c-MYC, SKP2, and early response gene mRNA (c-FOS, EGR1, c-MYC), and decreased p27, establishing that ADA3-driven c-MYC expression mediates its proliferative role. Ectopic overexpression, RT-PCR, Western blotting, cell proliferation assays Breast cancer research Medium 27852327

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation. The Journal of biological chemistry 190 11773077
1995 ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Molecular and cellular biology 158 7862114
2002 Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Molecular and cellular biology 116 12138191
1997 Identification of native complexes containing the yeast coactivator/repressor proteins NGG1/ADA3 and ADA2. The Journal of biological chemistry 105 9038164
1993 ADA3: a gene, identified by resistance to GAL4-VP16, with properties similar to and different from those of ADA2. Molecular and cellular biology 102 8413201
1997 ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3. Molecular and cellular biology 93 9154821
2001 hADA3 is required for p53 activity. The EMBO journal 66 11707411
2002 Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. The Journal of biological chemistry 53 12235159
1993 Characterization of NGG1, a novel yeast gene required for glucose repression of GAL4p-regulated transcription. The EMBO journal 47 8262068
2007 An essential role of human Ada3 in p53 acetylation. The Journal of biological chemistry 40 17272277
2020 The Ada2/Ada3/Gcn5/Sgf29 histone acetyltransferase module. Biochimica et biophysica acta. Gene regulatory mechanisms 36 32890768
2004 Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation. The Journal of biological chemistry 31 15496419
1996 Structure/functional properties of the yeast dual regulator protein NGG1 that are required for glucose repression. The Journal of biological chemistry 30 8621592
2007 hAda3 regulates p14ARF-induced p53 acetylation and senescence. Oncogene 29 17452980
2007 Expression and purification of recombinant yeast Ada2/Ada3/Gcn5 and Piccolo NuA4 histone acetyltransferase complexes. Methods (San Diego, Calif.) 28 17309836
2012 Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression. The Journal of biological chemistry 26 22736770
2007 Ada3 requirement for HAT recruitment to estrogen receptors and estrogen-dependent breast cancer cell proliferation. Cancer research 25 18089809
2008 hAda3 degradation by papillomavirus type 16 E6 correlates with abrogation of the p14ARF-p53 pathway and efficient immortalization of human mammary epithelial cells. Journal of virology 20 18256148
2008 Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function. The Biochemical journal 20 18377363
2007 Transcriptional adaptor ADA3 of Drosophila melanogaster is required for histone modification, position effect variegation, and transcription. Molecular and cellular biology 20 17967867
2018 Down-regulation of a pro-apoptotic pathway regulated by PCAF/ADA3 in early stage gastric cancer. Cell death & disease 19 29670108
2014 High-risk HPV16E6 stimulates hADA3 degradation by enhancing its SUMOylation. Carcinogenesis 18 24795430
2012 Alteration/deficiency in activation-3 (Ada3) plays a critical role in maintaining genomic stability. Cell cycle (Georgetown, Tex.) 18 23095635
2017 Epidermal Growth Factor Receptor activation promotes ADA3 acetylation through the AKT-p300 pathway. Cell cycle (Georgetown, Tex.) 15 28759294
2016 Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation. Molecular and cellular biology 15 27402865
2007 hADA2a and hADA3 are required for acetylation, transcriptional activity and proliferative effects of beta-catenin. Cancer biology & therapy 14 18059173
2015 Alteration/Deficiency in Activation 3 (ADA3) Protein, a Cell Cycle Regulator, Associates with the Centromere through CENP-B and Regulates Chromosome Segregation. The Journal of biological chemistry 13 26429915
2014 A functional genomics screen identifies PCAF and ADA3 as regulators of human granzyme B-mediated apoptosis and Bid cleavage. Cell death and differentiation 12 24464226
2016 ADA3 regulates normal and tumor mammary epithelial cell proliferation through c-MYC. Breast cancer research : BCR 11 27852327
2002 ADA3-containing complexes associate with estrogen receptor alpha. Nucleic acids research 11 12034840
2013 Identification of transcriptional and phosphatase regulators as interaction partners of human ADA3, a component of histone acetyltransferase complexes. The Biochemical journal 10 23167988
2017 Histone acetyltransferase encoded by NGG1 is required for morphological conversion and virulence of Candida albicans. Future microbiology 9 29110536
2010 Human ADA3 regulates RARalpha transcriptional activity through direct contact between LxxLL motifs and the receptor coactivator pocket. Nucleic acids research 9 20413580
2009 HPV16 E6-induced and E6AP-dependent inhibition of the transcriptional coactivator hADA3 in human cervical carcinoma cells. Cancer investigation 9 19194825
2022 Deletion of NGG1 in a recombinant Saccharomyces cerevisiae improved xylose utilization and affected transcription of genes related to amino acid metabolism. Frontiers in microbiology 6 36160216
2023 The Gcn5-Ada2-Ada3 histone acetyltransferase module has divergent roles in pathogenesis of Candida glabrata. Medical mycology 5 36715154
2023 Ada2 and Ada3 Regulate Hyphal Growth, Asexual Development, and Pathogenicity in Beauveria bassiana by Maintaining Gcn5 Acetyltransferase Activity. Microbiology spectrum 4 37052485
2016 Tale of a multifaceted co-activator, hADA3: from embryogenesis to cancer and beyond. Open biology 4 27605378

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