Affinage

TADA3

Transcriptional adapter 3 · UniProt O75528

Length
432 aa
Mass
48.9 kDa
Annotated
2026-04-28
38 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TADA3 (ADA3/NGG1) is an essential scaffolding subunit of the Ada2/Ada3/Gcn5 histone acetyltransferase (HAT) catalytic module within SAGA-type coactivator complexes, where it enables Gcn5-dependent nucleosomal histone acetylation at H3K9, H3K14, and H4K12 and expands Gcn5 lysine specificity (PMID:11773077, PMID:17967867). Beyond its core HAT-enabling role, TADA3 functions as a transcriptional coactivator adaptor that directly recruits HATs (p300, PCAF, Gcn5) to promoters occupied by transcription factors including p53, ERα, RARα, RXRα, and β-catenin, thereby coupling activator-dependent gene expression programs to chromatin acetylation (PMID:15496419, PMID:18089809, PMID:20413580, PMID:18059173). TADA3 stabilizes p53 by promoting its p300-mediated acetylation following DNA damage, is required for DNA damage response fidelity and chromosome segregation through interaction with centromeric CENP-B, and its own stability is regulated by acetylation–ubiquitination competition on shared lysine residues downstream of EGFR–AKT–p300 signaling (PMID:17272277, PMID:23095635, PMID:26429915, PMID:28759294). HPV16 E6 oncoprotein subverts multiple TADA3-dependent tumor-suppressive pathways by targeting TADA3 for SUMOylation-coupled E6AP-mediated ubiquitin-proteasomal degradation (PMID:24795430, PMID:12138191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1993 High

    Establishing that ADA3 functions in the same transcriptional coactivation pathway as ADA2 resolved a key question about whether multiple ADA genes act in parallel or sequential steps, placing ADA3 as a core component of an adaptor complex linking acidic activation domains to the transcription machinery.

    Evidence Genetic screen for GAL4-VP16 toxicity suppressors and double-mutant epistasis analysis in yeast

    PMID:8413201

    Open questions at the time
    • Biochemical nature of the ADA2–ADA3 interaction not yet defined
    • No enzymatic activity assigned to ADA3
  2. 1995 High

    Reconstituting the Ada2/Ada3/Gcn5 heterotrimer in vitro and mapping Ada3 domain architecture answered how these three proteins physically assemble, revealing Ada2 as the linchpin and identifying separable N- and C-terminal functional domains in Ada3.

    Evidence In vitro pulldown/reconstitution with recombinant proteins, deletion analysis, LexA fusion activation assays in yeast

    PMID:7862114

    Open questions at the time
    • Whether the heterotrimer is sufficient for HAT activity was unknown
    • Identity of in vivo native complexes containing Ada3 not resolved
  3. 1997 High

    Demonstrating that Ada3/Ada2 reside in multiple native complexes of distinct sizes (>2 MDa, ~900 kDa, ~200 kDa) and interact with TBP established that Ada3 functions within megadalton coactivator assemblies that directly contact basal transcription machinery.

    Evidence Co-immunoprecipitation from yeast extracts, gel-filtration and ion-exchange chromatography, domain deletion mapping of TBP interaction

    PMID:9038164

    Open questions at the time
    • Composition of the distinct complexes not fully defined
    • Functional distinction between the different-sized complexes unclear
  4. 2001 High

    Reconstituting the Ada2/Ada3/Gcn5 trimeric core as necessary and sufficient for nucleosomal HAT activity definitively established Ada3 as an essential enabler of Gcn5-mediated chromatin acetylation with expanded lysine specificity, answering why Ada3 loss abolishes histone acetylation in vivo.

    Evidence In vitro reconstitution of catalytic core, nucleosomal HAT assays with recombinant and native complexes

    PMID:11773077

    Open questions at the time
    • Structural basis of how Ada3 alters Gcn5 substrate specificity unknown
    • Whether mammalian ADA3 functions identically in HAT module not tested
  5. 2001 High

    Identifying hADA3 as a physical interactor and functional coactivator of p53 that is enhanced by DNA damage-induced phosphorylation revealed the first direct link between the SAGA adaptor module and a mammalian tumor suppressor.

    Evidence Yeast p53 dissociator assay, co-immunoprecipitation from human cells, DNA damage experiments, transcriptional reporters, apoptosis assays

    PMID:11707411

    Open questions at the time
    • Mechanism by which hADA3 promotes p53 transcriptional output not defined
    • Whether HAT activity is required for p53 coactivation unknown
  6. 2002 High

    Showing that HPV16 E6 targets hADA3 for degradation and that E6 mutants unable to degrade p53 but able to target hADA3 still abrogate p53 function established hADA3 as an independent viral target whose loss is sufficient to disable p53-mediated tumor suppression.

    Evidence Co-immunoprecipitation, protein degradation assays, E6 mutant panel, cell cycle analysis

    PMID:12138191

    Open questions at the time
    • Degradation pathway (ubiquitin ligase identity, PTM requirements) not defined
    • Whether E6 targets hADA3 in patient-derived HPV-positive cells not shown
  7. 2002 High

    Demonstrating that hADA3 directly binds RXRα and is recruited to retinoid response elements expanded the coactivator function of TADA3 beyond p53 to nuclear receptors, establishing it as a general transcription factor adaptor.

    Evidence GST pulldown, co-immunoprecipitation, ChIP on p21 promoter, transcriptional reporter assays

    PMID:12235159

    Open questions at the time
    • Whether hADA3 directly contacts RXRα or does so through an intermediary in the full complex was debated (cf. PMID:12034840)
    • Structural basis of receptor recognition unknown
  8. 2004 High

    Confirming direct hADA3–ERα/ERβ interaction and showing that endogenous hADA3 is required for estrogen-dependent target gene expression resolved the question of whether hADA3 serves as a bona fide nuclear receptor coactivator for estrogen signaling.

    Evidence GST pulldown, co-immunoprecipitation, ChIP on pS2 promoter, siRNA knockdown, RT-PCR for endogenous targets

    PMID:15496419

    Open questions at the time
    • Whether hADA3 interaction with ERα is direct in the context of intact SAGA/ATAC not clarified
    • Contribution to ER-driven oncogenesis not tested in vivo
  9. 2007 High

    Mechanistically linking hADA3 to p53 stabilization through p300-mediated acetylation and ARF-induced senescence resolved how hADA3 promotes p53 function: by serving as a scaffold that facilitates p300-dependent p53 acetylation, which prevents p53 degradation.

    Evidence Overexpression and shRNA knockdown of hAda3, p53 acetylation site mutants, p14ARF-induced senescence assays, dominant-negative N-terminal domain

    PMID:17272277 PMID:17452980

    Open questions at the time
    • Whether hADA3 directly bridges p53 and p300 or acts through additional intermediaries not distinguished
    • In vivo tumor suppressor role not validated
  10. 2007 High

    Showing that Ada3 co-sediments with ERα and three distinct HATs (p300, PCAF, Gcn5) and is required for their ligand-dependent promoter recruitment established Ada3 as the central hub coordinating multiple HATs at hormone-responsive genes.

    Evidence Glycerol gradient cosedimentation, co-immunoprecipitation, ChIP, shRNA knockdown, proliferation assays in ER-positive breast cancer cells

    PMID:18089809

    Open questions at the time
    • Stoichiometry of the multi-HAT complex undefined
    • Whether Ada3 bridges HATs simultaneously or sequentially unclear
  11. 2007 High

    Drosophila genetic analysis showed that dADA3 localizes to chromosomes, depends on dGcn5/dAda2a for stability, and is required for H3K9/K14 and H4K12 acetylation, confirming evolutionary conservation of Ada3's HAT-enabling function from yeast to metazoans.

    Evidence Immunofluorescence on polytene chromosomes, genetic mutant analysis, western blot for histone marks in Drosophila

    PMID:17967867

    Open questions at the time
    • Whether Drosophila Ada3 also serves as a transcription factor adaptor not tested
    • Target gene specificity not addressed
  12. 2007 High

    Discovering that hADA3 interacts with β-catenin at the c-Myc enhancer and is required for Wnt target gene activation extended TADA3 function to the Wnt signaling pathway, beyond nuclear receptor and p53 programs.

    Evidence Co-immunoprecipitation with domain mapping, ChIP at c-Myc enhancer, siRNA knockdown, RT-PCR for Wnt targets

    PMID:18059173

    Open questions at the time
    • Whether β-catenin acetylation by TADA3-associated HATs has functional consequences in vivo unclear
    • Specificity versus other TCF/LEF coactivators not assessed
  13. 2010 High

    Identifying LxxLL motifs in hADA3 as mediating hormone-dependent direct interaction with the RARα coactivator pocket answered how TADA3 physically recognizes nuclear receptors and established a general structural mechanism for its adaptor function.

    Evidence LxxLL motif mutagenesis (loss and gain of function), co-immunoprecipitation, ChIP on RARβ2 promoter, endogenous target gene expression

    PMID:20413580

    Open questions at the time
    • Crystal structure of ADA3 LxxLL–receptor interface not solved
    • Whether different LxxLL motifs specify different receptor interactions not fully resolved
  14. 2012 High

    Mouse knockout studies established that Ada3 is essential for embryonic development and cell proliferation, with deletion causing G1/S delay via p27 accumulation (due to reduced c-Myc), global histone acetylation loss, mitotic defects, chromosomal aberrations, and impaired DNA damage repair, consolidating Ada3 as essential for genome integrity.

    Evidence Germline Ada3 knockout, conditional deletion in MEFs, FACS cell cycle analysis, human Ada3 rescue, cytogenetics, DNA damage foci kinetics

    PMID:22736770 PMID:23095635

    Open questions at the time
    • Tissue-specific roles in adult mouse not explored
    • Whether DNA repair defect is direct or secondary to chromatin acetylation loss unclear
  15. 2014 High

    Defining the SUMOylation–ubiquitination coupling mechanism for HPV16 E6-mediated hADA3 degradation via E6AP resolved a longstanding question about the degradation pathway and revealed that SUMOylation primes hADA3 for ubiquitin-dependent destruction.

    Evidence Ubiquitination and SUMOylation assays, siRNA knockdown of E6AP and Ubc9, protein stability assays

    PMID:24795430

    Open questions at the time
    • SUMO acceptor lysine sites on hADA3 not mapped
    • Whether this mechanism operates for other E6 targets unknown
  16. 2014 High

    Identifying a PCAF/ADA3→PACS2→Bid pathway for granzyme B-induced mitochondrial apoptosis revealed a non-transcriptional role for the PCAF/ADA3 module in immune cell-mediated killing.

    Evidence shRNAmiR functional genomic screen, independent siRNA validation, cytochrome c release and Bid cleavage assays, PACS2 epistasis

    PMID:24464226

    Open questions at the time
    • Whether ADA3's role in this pathway requires its HAT-scaffolding function not tested
    • In vivo relevance to anti-tumor immunity not established
  17. 2015 High

    Discovering that ADA3 physically associates with CENP-B at centromeres and is required for CENP-B loading and proper chromosome segregation revealed an unexpected centromeric function beyond transcriptional coactivation.

    Evidence Proximity ligation assay, immunofluorescence, ChIP on α-satellite sequences, CENP-B binding-deficient ADA3 mutant rescue, cytogenetics

    PMID:26429915

    Open questions at the time
    • Whether centromeric function involves local histone acetylation not determined
    • Structural basis of ADA3–CENP-B interaction not solved
  18. 2016 High

    Demonstrating that ADA3 itself is dynamically acetylated by GCN5/PCAF/p300 and deacetylated by SIRT1, and that acetylation-defective ADA3 mutants fail to restore histone acetylation or proliferation, established that ADA3 acetylation is a regulatory switch controlling its HAT complex function.

    Evidence Mass spectrometry for acetylation sites, site-directed mutagenesis, functional rescue in Ada3-deleted MEFs, co-immunoprecipitation

    PMID:27402865

    Open questions at the time
    • How acetylation mechanistically alters ADA3 function (conformational change, binding affinity) undefined
    • Cell cycle-dependent regulation mechanism not elucidated
  19. 2017 High

    Placing ADA3 acetylation downstream of EGFR–AKT–p300 signaling and showing that acetylation competes with ubiquitination on shared lysine residues to control ADA3 stability connected growth factor signaling to chromatin acetylation through a post-translational switch on ADA3.

    Evidence RTK inhibitor (lapatinib) and AKT inhibitor treatment, acetylation-defective K→R mutants, protein half-life assays, cell cycle analysis

    PMID:28759294

    Open questions at the time
    • Identity of the E3 ubiquitin ligase targeting ADA3 under normal (non-HPV) conditions unknown
    • In vivo validation of EGFR–ADA3 axis in tumors lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis by which ADA3 enables Gcn5 nucleosomal substrate recognition and expanded lysine specificity, whether ADA3's centromeric and DNA damage repair functions are mechanistically separable from its HAT-scaffolding role, and identification of the physiological E3 ligase controlling ADA3 turnover in the absence of viral oncoproteins.
  • No high-resolution structure of ADA3 in the HAT module context
  • Centromeric versus transcriptional functions not genetically separated
  • Physiological E3 ubiquitin ligase for ADA3 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
CENPBCTNNB1EP300GCN5PCAFTADA2ATADA2BTP53
Complex memberships
ADA complexAda2/Ada3/Gcn5 HAT moduleSAGA complexTFTC/STAGA complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 ADA3 (NGG1) was identified as a gene whose mutation prevents GAL4-VP16 toxicity and reduces transactivation by VP16 and GCN4 acidic activation domains; double disruption of ada2 and ada3 shows no additive growth defect, placing them in the same pathway. Genetic screen, gene disruption, epistasis analysis (double mutant), in vitro transcription initiation assay Molecular and cellular biology High 8413201
1995 Ada2, Ada3, and Gcn5 form a heterotrimeric complex in vitro, with Ada2 as the linchpin holding Ada3 and Gcn5 together; Ada3 has two separable domains, with the C-terminal domain sufficient for complex formation and the N-terminal domain proposed to mediate interaction with activation domains. In vitro pulldown/reconstitution, deletion analysis, in vivo LexA fusion activation assays Molecular and cellular biology High 7862114
1997 NGG1p/ADA3p and ADA2p are coimmunoprecipitated from yeast whole cell extracts, are present in at least four native complexes of different sizes (>2 MDa, ~900 kDa, ~200 kDa), and the complex associates with TBP; this TBP interaction requires residues 274–307 of NGG1p. Co-immunoprecipitation from yeast extracts, ion-exchange chromatography, gel-filtration chromatography, deletion analysis The Journal of biological chemistry High 9038164
2001 Yeast Ada2, Ada3, and Gcn5 form the catalytic core of ADA and SAGA HAT complexes that is necessary and sufficient in vitro for nucleosomal HAT activity and lysine specificity; Ada3 is required for Gcn5-dependent nucleosomal HAT activity and facilitates an expanded lysine specificity, while Ada2 potentiates Gcn5 catalytic activity. In vitro reconstitution of catalytic core, nucleosomal HAT activity assays, yeast extract-based 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 events in the p53 N-terminus; hADA3 is required for full transcriptional activity of p53 and p53-mediated apoptosis. Yeast p53 dissociator assay, co-immunoprecipitation from human cells, DNA damage experiments, transcriptional reporter assays, apoptosis assays The EMBO journal High 11707411
2002 hADA3 is a novel interacting partner and target of HPV16 E6 oncoprotein; E6 induces hADA3 degradation; hADA3 functions as a coactivator for p53-mediated transactivation by stabilizing p53; E6 mutants that do not degrade p53 but do interact with hADA3 still abrogate p53-mediated transactivation and G1 arrest after DNA damage. Co-immunoprecipitation, protein degradation assays, transcriptional reporter assays, cell cycle analysis (G1 arrest), use of E6 mutants Molecular and cellular biology High 12138191
2002 hADA3 directly binds RXRα in vitro and in vivo, is recruited to native RXR response elements in the p21 promoter (by ChIP), and enhances RXRα-mediated transactivation of retinoid target genes; HPV E6 inhibits this RXR-mediated transactivation by targeting hADA3. GST pulldown (in vitro binding), co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transcriptional reporter assays The Journal of biological chemistry High 12235159
2002 ADA3-containing TFTC complex interacts with ERα in a ligand-independent manner; mouse mADA3 does not directly interact with nuclear receptors despite containing LxxLL NR boxes, indicating other TFTC subunits mediate the receptor interaction. Cloning of mouse ADA3, co-immunoprecipitation, interaction assays with ERα Nucleic acids research Medium 12034840
2004 hADA3 directly interacts with ERα and ERβ in vitro and in vivo; hADA3 is a component of activator complexes bound to the native ER response element in the pS2 promoter; endogenous hADA3 is required for ER-mediated transactivation and estrogen-induced target gene expression; HPV E6 targeting of hADA3 inhibits ERα-mediated transactivation. GST pulldown, co-immunoprecipitation, ChIP, luciferase reporter assay, RT-PCR for endogenous ER target genes, RNA interference (siRNA knockdown of ADA3) The Journal of biological chemistry High 15496419
2007 Endogenous hAda3 stabilizes p53 protein by promoting its acetylation at p300/CBP acetylation sites; hAda3 is required for DNA damage-induced p53 acetylation, stabilization, and target gene induction; acetylation-defective p53 mutants fail to show hAda3-dependent stabilization. Inducible overexpression and shRNA knockdown of hAda3, western blot for p53 acetylation, p53 mutant analysis, target gene expression assays The Journal of biological chemistry High 17272277
2007 hAda3 is required for p14ARF-induced p53 acetylation and cellular senescence; the N-terminal domain of hAda3 binds p53 but not p300, and its expression blocks p14ARF-induced p53 acetylation and senescence; hAda3 promotes p300-mediated p53 acetylation and siRNA knockdown of hAda3 inhibits endogenous p53 acetylation and p21 accumulation. Dominant-negative N-terminal domain expression, siRNA knockdown, p300-mediated acetylation assay, senescence assay, western blot Oncogene High 17452980
2007 Ada3, ERα, and three distinct HATs (p300, PCAF, and Gcn5) co-sediment in a complex (glycerol gradient) and co-immunoprecipitate; Ada3 is required for ligand-dependent recruitment of p300, PCAF, and Gcn5 to the ER-responsive pS2 promoter; Ada3 is critical for estrogen-dependent proliferation of ER-positive breast cancer cells. Glycerol gradient cosedimentation, co-immunoprecipitation, ChIP, shRNA knockdown, 2D and 3D cell proliferation assays Cancer research High 18089809
2007 Drosophila dADA3 localizes to chromosomes and is significantly reduced in dGcn5 and dAda2a mutant backgrounds; dAda3 loss reduces acetylation at H3K9, H3K14, H4K12, and phosphorylation at H3S10; dAda3 is required for oogenesis and somatic cell viability. Immunofluorescence (localization), genetic mutant analysis, western blot for histone modifications, position effect variegation assays Molecular and cellular biology High 17967867
2007 hADA2a and hADA3 physically interact with beta-catenin through Armadillo repeats 6–12 and the C-terminal transactivation domain; both 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 Wnt target gene activation and proliferation. Co-immunoprecipitation, domain deletion analysis, ChIP, siRNA knockdown, luciferase reporter assay, RT-PCR for endogenous target genes Cancer biology & therapy High 18059173
2008 ANCO-1 and ANCO-2 interact with hADA3; the interaction occurs between the conserved C-terminal domain of ANCO-1 and the N-terminal transactivation domain of ADA3; ANCO-1 co-localizes with ADA3, ADA2α/β, and PCAF at nuclear dots; ANCO-1/2 repress ADA3-mediated transcriptional co-activation on nuclear receptors. Co-immunoprecipitation, domain deletion analysis, immunofluorescence co-localization, transcriptional reporter assay The Biochemical journal Medium 18377363
2010 Human ADA3 interacts directly with RARα in a hormone-dependent manner through LxxLL motifs in hADA3 and the coactivator pocket of RARα; loss- and gain-of-function mutations in LxxLL motifs alter this interaction; hADA3 associates with RARα target gene promoters in a hormone-dependent manner; ADA3 knockdown impairs RARβ2 expression. Co-immunoprecipitation, LxxLL motif mutagenesis (loss/gain of function), ChIP, RT-PCR for endogenous target genes, structural modeling Nucleic acids research High 20413580
2012 Germline deletion of Ada3 in mouse causes embryonic lethality; conditional deletion in MEFs causes severe proliferation defect rescued by human Ada3; Ada3 deletion causes G1-to-S delay due to accumulation of CDK inhibitor p27 as an indirect consequence of reduced c-Myc transcription; Ada3 loss causes global histone acetylation changes, abnormal nuclei, mitotic defects, and delayed G2/M-to-G1 transition. Germline knockout (Ada3 null mouse), adenovirus-Cre conditional deletion in MEFs, cell cycle analysis (FACS), ectopic rescue with human Ada3, siRNA knockdown of p27, microarray gene expression analysis, immunofluorescence The Journal of biological chemistry High 22736770
2012 Ada3 deletion leads to enhanced chromosomal aberrations (breaks, fragments, deletions, translocations) and delayed clearance of DNA damage foci (pATM, γH2AX, p53BP1, pRAD51) after ionizing radiation, demonstrating a role in DNA damage response and genomic stability maintenance. Adenovirus-Cre conditional deletion in Ada3fl/fl MEFs, immunofluorescence for DNA damage foci, chromosomal aberration analysis, comet assay Cell cycle (Georgetown, Tex.) High 23095635
2013 hADA3 interacts with AATF (apoptosis-antagonizing transcription factor), PPP1R7 (PP1 regulatory subunit 7), and PPP2R5D (PP2A regulatory subunit δ) as novel binding partners; interaction with these partners does not require the C-terminal ADA2-interacting domain of hADA3; expression of these interacting proteins alters hADA3-regulated reporter gene activity. Yeast two-hybrid screen of human cDNA library, co-immunoprecipitation, immunofluorescence co-localization, truncation analysis, reporter gene assay The Biochemical journal Medium 23167988
2014 PCAF and ADA3 regulate granzyme B-mediated apoptosis upstream of mitochondrial permeabilization; PCAF or ADA3 knockdown reduces Bid cleavage and PACS2 expression; PACS2 knockdown phenocopies PCAF/ADA3 knockdown, defining a PCAF/ADA3→PACS2→Bid pathway for mitochondrial apoptosis. shRNAmiR functional genomic screen, siRNA knockdown validation, cytochrome c release assay, Bid cleavage assay, PACS2 expression analysis 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 by HPV16 E6 and makes hADA3 unstable; Ubc9 depletion prevents rapid E6-mediated hADA3 degradation, revealing a SUMOylation-ubiquitination coupling mechanism. Ubiquitination assay, SUMOylation assay, siRNA knockdown of E6AP and Ubc9, western blot, protein stability assays Carcinogenesis High 24795430
2015 ADA3 associates with the α-satellite repeat region of human X chromosome centromeres; ADA3 physically associates with CENP-B through its N-terminus (confirmed by proximity ligation assay and immunofluorescence); an ADA3 mutant unable to bind CENP-B fails to rescue cell proliferation; ADA3 is required for loading CENP-B onto centromeres; Ada3 deletion causes chromosome segregation defects. Proximity ligation assay, immunofluorescence, ChIP on centromeric sequences, deletion analysis, CENP-B binding-deficient mutant rescue assay, cytogenetic analysis of chromosome segregation The Journal of biological chemistry High 26429915
2016 ADA3 acetylation is dynamically regulated in a cell cycle-dependent manner by HATs GCN5, PCAF, and p300, and is reversed by SIRT1; mass spectrometry and site-directed mutagenesis identified major acetylation sites; acetylation-defective ADA3 mutants associate with HATs and HAT complex components but fail to restore global or locus-specific histone acetylation marks or cell proliferation in Ada3-deleted MEFs. Mass spectrometry to identify acetylation sites, site-directed mutagenesis, inducible expression in Ada3-deleted MEFs, rescue assay, HAT activity assays, co-immunoprecipitation Molecular and cellular biology High 27402865
2017 EGFR/HER2 signaling through AKT promotes phosphorylation of p300, which in turn promotes ADA3 acetylation; inhibition of HER1/HER2 by lapatinib reduces phospho-AKT, p300 phosphorylation, and ADA3 protein levels; ADA3 acetylation competes with ubiquitination on shared lysine residues to regulate ADA3 stability; ADA3 knockdown mimics lapatinib-induced cell cycle inhibition and apoptosis. RTK inhibitor (lapatinib) treatment, AKT inhibition, p300/PCAF inhibitor (garcinol), acetylation-defective ADA3 mutants (K→R), protein stability (half-life) assays, cell cycle analysis Cell cycle (Georgetown, Tex.) High 28759294

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 114 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 35 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 12 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