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Showing AATF — BFR2 is a alias.

AATF

Protein AATF · UniProt Q9NY61

Length
560 aa
Mass
63.1 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AATF/Che-1 is a multifunctional nuclear phosphoprotein that integrates transcriptional control of proliferation, the DNA damage response, and apoptosis (PMID:12450794, PMID:17157788). It binds RNA polymerase II subunit hRPB11 and the retinoblastoma protein, and in proliferating cells it competes with HDAC1 for the Rb pocket—displacing HDAC1 from Rb/E2F complexes and from Sp1 sites to activate E2F targets and p21WAF1/CIP1 with accumulation of acetylated histone H3 (PMID:10783144, PMID:12450794, PMID:12847090). This pro-proliferative chromatin activity depends on direct histone binding, which requires CK2 phosphorylation at Ser316/Ser320/Ser321 and is reinforced by displacement of class I HDACs to sustain global histone acetylation and BRD4 recruitment (PMID:33186461, PMID:34266450). Upon genotoxic stress, AATF is phosphorylated and stabilized by ATM/ATR and Chk2 and PARylated by PARP-1, accumulating and switching its promoter occupancy from rDNA and E2F loci to the TP53 and p21 promoters to activate growth-arrest p53 target genes and maintain cell-cycle checkpoints (PMID:17157788, PMID:21317046, PMID:25996291, PMID:32421830). AATF restrains apoptosis through multiple routes: MK2 phosphorylation releases it to the nucleus where it represses p53-driven PUMA/BAX/BAK transcription, and it sustains XIAP and mutant p53 expression (PMID:18049476, PMID:20708154, PMID:22909821). Its own abundance is controlled by Pin1- and HIPK2-dependent priming of HDM2-mediated ubiquitylation and proteasomal degradation during apoptosis (PMID:17468107, PMID:25210797). In the nucleolus AATF supports ribosome biogenesis, forming the ANN complex with NGDN and NOL10 required for 18S rRNA maturation and 40S subunit synthesis and promoting RNA Pol I/UBF-dependent rDNA transcription (PMID:27599843, PMID:32421830). It additionally stabilizes the NHEJ factor XRCC4 until ATM phosphorylation at Ser189 releases it for recruitment to DNA breaks, and localizes to paraspeckles via NEAT1_2 to resolve R-loops and suppress interferon activation (PMID:35929179, PMID:40436899). These activities make AATF a driver of tumor proliferation in vivo, including Kras-driven lung adenocarcinoma in a p53-dependent manner and plasma-cell multiple myeloma (PMID:29321668, PMID:33186461).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Establishing AATF's existence and its first functional theme—antagonism of apoptosis—anchored all later work by linking it to a death kinase and to transcription.

    Evidence Yeast two-hybrid against Dlk/ZIP kinase plus Gal4-BD transactivation and apoptosis-interference assays

    PMID:10580117

    Open questions at the time
    • No direct DNA targets identified
    • Domain requirements for transactivation undefined
  2. 2003 High

    Defining AATF as an HDAC1-displacing cofactor at Rb/E2F and Sp1 sites explained how it drives proliferation and p53-independent p21 activation through chromatin acetylation.

    Evidence Co-IP, ChIP, and RNAi in Rb-proficient vs Rb-deficient cells; ChIP and reporter assays on the p21/Sp1 promoter

    PMID:10783144 PMID:12450794 PMID:12847090

    Open questions at the time
    • Direct vs indirect promoter recruitment mechanism not fully resolved
    • Phospho-regulation of HDAC1 competition not yet known at this stage
  3. 2007 High

    Identifying ATM/ATR/Chk2 phosphorylation as a switch that stabilizes AATF and redirects it to TP53/p21 promoters established its role as a damage-responsive checkpoint activator.

    Evidence Co-IP of kinase-substrate, ChIP of promoter recruitment, cell-cycle flow cytometry, RNAi

    PMID:17157788

    Open questions at the time
    • Exact phospho-residues not mapped
    • Mechanism of promoter selectivity unresolved
  4. 2007 High

    Mapping Pin1-primed, HDM2-mediated ubiquitylation showed how AATF protein levels are downregulated to permit apoptosis, defining its turnover control.

    Evidence Co-IP, ubiquitination assay, half-life measurement, Pin1-binding mutant, apoptosis assay

    PMID:17468107

    Open questions at the time
    • Phospho-sites recognized by Pin1 not defined here
    • Other E3 ligases not excluded
  5. 2011 High

    Demonstrating PARP-1-dependent PARylation as an ATM-independent route to AATF stabilization revealed a parallel damage signal converging on its promoter occupancy.

    Evidence Co-IP, in vitro PARylation, ChIP at p21 promoter, PARP inhibitor/knockout and ATM-inhibitor epistasis

    PMID:21317046

    Open questions at the time
    • PARylation acceptor residues not mapped
    • Interplay with phosphorylation marks unresolved
  6. 2012 High

    Identifying MK2 phosphorylation as the trigger for cytoplasm-to-nucleus translocation and repression of PUMA/BAX/BAK promoters explained how AATF actively blocks p53-driven apoptosis and confers chemoresistance.

    Evidence MK2 kinase assay, MRLC3 Co-IP, fractionation, ChIP, phospho-mimic mutagenesis, xenografts

    PMID:22909821

    Open questions at the time
    • How nuclear AATF selects pro-apoptotic vs growth-arrest p53 loci unclear
    • Relationship to ATM/Chk2 signaling not integrated
  7. 2015 High

    Direct p53 binding forming a p53/Brca1 ternary complex that biases transactivation toward growth-arrest genes, confirmed in Che-1(+/-) mice, established AATF as a determinant of the arrest-versus-death p53 decision.

    Evidence Co-IP, genome-wide ChIP-seq, heterozygous knockout mice with irradiation phenotype

    PMID:25996291

    Open questions at the time
    • Structural basis of p53 target selectivity unknown
    • How interaction is lost during apoptosis not mechanistically defined
  8. 2014 High

    Adding HIPK2 as a stress kinase that primes AATF for HDM2-dependent degradation completed the picture of how genotoxic signaling tips AATF abundance toward apoptosis.

    Evidence Co-IP, in vitro kinase assay, ubiquitylation assay, RNAi, apoptosis rescue

    PMID:25210797

    Open questions at the time
    • HIPK2 target residues on AATF not specified
    • Coordination with Pin1/CK2 phosphorylation unresolved
  9. 2016 High

    Discovery of the ANN complex (AATF-NGDN-NOL10) localized a major non-transcriptional role to nucleolar ribosome biogenesis.

    Evidence IP-MS, domain mapping, RNAi with rRNA processing analysis, immunofluorescence

    PMID:27599843

    Open questions at the time
    • Molecular function of AATF within the complex (catalytic vs scaffold) undefined
    • Link between ribosome biogenesis and stress signaling not established
  10. 2020 High

    Linking AATF to RNA Pol I/UBF-driven rDNA transcription, with damage-induced re-localization from rDNA to TP53, unified its nucleolar and checkpoint roles into a stress-responsive promoter switch.

    Evidence Co-IP with Pol I/UBF, ChIP at rDNA, reporter assay, pre-rRNA Northern, immunofluorescence

    PMID:32421830

    Open questions at the time
    • Signal driving rDNA-to-TP53 relocalization not defined
    • Relationship to ANN complex function unclear
  11. 2021 High

    Mapping CK2 phosphorylation at Ser316/320/321 as a requirement for histone H3 binding provided the molecular basis for AATF's pro-proliferative chromatin acetylation activity.

    Evidence In vitro CK2 kinase assay, mutagenesis, 2D gel/MS phospho-site mapping, Co-IP, proliferation assay

    PMID:33186461 PMID:34266450

    Open questions at the time
    • Structural mode of histone engagement undefined
    • Whether other kinases regulate this interaction unknown
  12. 2022 High

    Localization to NEAT1_2 paraspeckles and R-loops, with R-loop accumulation and interferon induction upon depletion, revealed a genome-stability role coupling AATF to innate immune suppression.

    Evidence NEAT1 RNA-IP, S9.6 R-loop dot blot/IF, RNAi, RNA-seq IFN signature, ChIP

    PMID:35929179

    Open questions at the time
    • Direct enzymatic activity on R-loops not demonstrated
    • Mechanism of R-loop resolution by AATF unresolved
  13. 2025 High

    Identifying ATM-Ser189 phosphorylation as the release signal that frees stabilized XRCC4 for recruitment to breaks placed AATF directly within NHEJ repair.

    Evidence Co-IP, ATM kinase assay, phospho-site mutagenesis, NHEJ and ubiquitination assays, xenograft

    PMID:40436899

    Open questions at the time
    • Generality across cell types beyond glioma stem-like cells untested
    • Coordination with AATF's transcriptional damage response unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AATF's many post-translational modifications (ATM/ATR, Chk2, MK2, CK2, HIPK2 phosphorylation; PARylation; ubiquitylation) are hierarchically integrated to dictate its localization and the choice among proliferation, arrest, apoptosis suppression, and repair remains unresolved.
  • No unified model of combinatorial PTM control
  • No structural framework for its distinct binding interfaces
  • Tissue-specific determinants of functional output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0042393 histone binding 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 4 GO:0005730 nucleolus 3 GO:0005829 cytosol 2 GO:0005654 nucleoplasm 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 3 R-HSA-8953854 Metabolism of RNA 2
Partners
HDAC1HDM2NGDNPARP1PIN1RB1TP53XRCC4
Complex memberships
ANN complex (AATF-NGDN-NOL10)RNA polymerase I/UBF rDNA transcription complexSAGA HAT module

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 AATF (apoptosis antagonizing transcription factor) was identified as a binding partner of Dlk/ZIP kinase (a serine/threonine kinase) via yeast two-hybrid and shown to interfere with Dlk-induced apoptosis. AATF contains an acidic domain and putative leucine zipper and exhibits transcriptional transactivation activity as a Gal4-BD fusion protein. Yeast two-hybrid interaction screen, transactivation assay (Gal4-BD fusion), apoptosis interference assay FEBS letters Medium 10580117
2000 Che-1/AATF interacts with RNA polymerase II subunit hRPB11 and with the retinoblastoma protein (Rb) via two distinct domains, and functionally represses Rb's growth suppression by counteracting Rb-mediated inhibition of E2F1 transactivation. Co-immunoprecipitation, GST pulldown, transactivation reporter assay FASEB journal Medium 10783144
2002 Che-1/AATF contacts the Rb pocket region and competes with HDAC1 for the same Rb binding site, displacing HDAC1 from Rb/E2F complexes in vitro and from E2F target gene promoters in vivo, thereby activating DNA synthesis. Che-1-specific RNA interference reduces E2F activity and cell proliferation in Rb-proficient but not Rb-deficient cells. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), RNA interference, flow cytometry (DNA synthesis) Cancer cell High 12450794
2003 Che-1/AATF overexpression in colon carcinoma cells activates p21WAF1/CIP1 expression in a p53-independent manner by displacing HDAC1 from Sp1 binding sites on the p21 promoter and accumulating acetylated histone H3, causing G1 arrest. Che-1 RNAi reduces p21 transactivation and increases proliferation. Chromatin immunoprecipitation (ChIP), RNA interference, flow cytometry, reporter assay The Journal of biological chemistry High 12847090
2003 AATF colocalizes with Par-4 in cytoplasmic and nuclear compartments and interacts directly with Par-4 via the leucine zipper domain in neural cells. AATF/Par-4 complex formation is required for AATF to block Par-4-induced aberrant production and secretion of amyloid beta peptide 1-42. Co-immunoprecipitation, co-localization (immunofluorescence), ELISA for Aβ secretion, overexpression/co-expression assays The Journal of biological chemistry Medium 14627703
2003 Che-1/AATF directly interacts with Tau protein via Tau's amino-terminal region (not involved in microtubule binding) in rat cerebellar granule neurons, partially colocalizing in the cytoplasm; this interaction is modulated during neuronal apoptosis. Co-immunoprecipitation from neuronal lysates, FRET analysis, overexpression in COS-7 cells Molecular and cellular neurosciences Medium 14697667
2004 AATF overexpression in PC12 neural cells suppresses superoxide production, inhibits peroxynitrite formation and membrane lipid peroxidation, and protects against amyloid beta-peptide-induced apoptosis. Inhibition of AATF induction sensitizes cortical neurons to Aβ toxicity. Overexpression/knockdown in PC12 and cortical neurons, ROS assay, apoptosis assay Neurobiology of disease Medium 15207272
2006 Che-1/AATF contributes to the DNA damage response: checkpoint kinases ATM/ATR and Chk2 physically interact with Che-1 and phosphorylate it in response to DNA damage, leading to Che-1 accumulation, its specific recruitment to TP53 and p21 promoters, transcriptional activation of p53, and maintenance of the G2/M checkpoint. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), phosphorylation assay, flow cytometry (cell cycle), RNA interference Cancer cell High 17157788
2007 In response to apoptotic stimuli, Che-1/AATF interacts with the peptidyl-prolyl isomerase Pin1; Pin1-induced conformational changes are required for Che-1 interaction with E3 ubiquitin ligase HDM2, which promotes Che-1 ubiquitination and proteasomal degradation. A Che-1 mutant unable to bind Pin1 has increased half-life and reduced apoptosis. Co-immunoprecipitation, ubiquitination assay, half-life measurement, site-directed mutagenesis, apoptosis assay The Journal of biological chemistry High 17468107
2007 NRAGE overexpression inhibits nuclear localization of Che-1/AATF by sequestering it in the cytoplasm, and targets endogenous Che-1 for proteasome-dependent degradation. Che-1 overexpression completely reverts NRAGE-induced cell death, identifying them as functional antagonists. Co-immunoprecipitation, subcellular fractionation/localization (EGFP fusion), proteasome inhibitor rescue, cell death assay Journal of cell science Medium 17488777
2007 Che-1/AATF phosphorylation following DNA damage promotes XIAP expression in a NF-κB-dependent manner, and XIAP expression is required for the antiapoptotic activity of Che-1. Chromatin immunoprecipitation (ChIP), RNA interference, reporter assay, in vivo tumor xenograft with siRNA Cell death and differentiation Medium 18049476
2008 Che-1/AATF overexpression induces Cdk5 mRNA and protein expression, directly interacts with Cdk5 in vivo without competing with Cdk5/p35 binding (thus associating with the active kinase complex), and is itself a substrate of Cdk5 kinase. Co-immunoprecipitation, Western blot, in vitro kinase assay Neuroreport Medium 18388733
2009 AATF is induced by ER stress through the PERK-eIF2α pathway and transcriptionally activates AKT1 via STAT3, sustaining Akt1 activation and promoting cell survival. AATF knockdown sensitizes cells to ER stress-mediated death; ectopic AATF or constitutively active AKT1 confers resistance. Gene expression profiling, RNA interference, overexpression, Western blot, reporter assay Cell death and differentiation Medium 19911006
2010 Che-1/AATF is required for sustaining mutant p53 expression in cancer cell lines; Che-1 depletion by siRNA induces apoptosis in vitro and in vivo and activates DNA damage checkpoint response and p73 transactivation in mutant-p53-expressing cells. siRNA knockdown, ChIP, Western blot, in vivo xenograft Cancer cell Medium 20708154
2011 PARP-1 directly interacts with Che-1/AATF, promotes its poly(ADP-ribosyl)ation in vitro and in vivo, and stabilizes Che-1 after DNA damage independently of ATM kinase activity. Reduced PARP activity or PARP-1 knockout impairs Che-1 accumulation and its occupancy at the p21 promoter. Co-immunoprecipitation, in vitro PARylation assay, ChIP, PARP inhibitor/knockout, epistasis with ATM inhibitor DNA repair High 21317046
2012 Upon genotoxic stress, AATF/Che-1 is phosphorylated by MK2 (downstream of p38), which releases AATF from cytoplasmic MRLC3 and triggers nuclear translocation. Nuclear AATF binds PUMA, BAX, and BAK promoter regions to repress p53-driven transcription of pro-apoptotic genes. Phospho-mimicking AATF confers adriamycin resistance in vivo, while AATF-depleted tumors show enhanced drug response. Kinase assay (MK2), co-immunoprecipitation (MRLC3), subcellular fractionation, ChIP, site-directed mutagenesis, xenograft experiments The EMBO journal High 22909821
2012 AATF (nucleolar) acts as a cofactor required for c-Jun-mediated apoptosis. UV irradiation triggers AATF translocation from the nucleolus to the nucleus, where it physically associates with c-Jun. AATF overexpression or knockout levels proportionally alter c-Jun phosphorylation and expression of FasL and TNF-α. AATF mutants defective in c-Jun binding are also defective in AP-1 activity and apoptosis induction. Co-immunoprecipitation, subcellular localization (translocation assay), deletion mutagenesis, reporter assay, knockout MEFs Molecular biology of the cell High 22933572
2013 Che-1/AATF localizes to interphase centrosomes and accumulates there following DNA damage or spindle poisons. Che-1 depletion generates supernumerary centrosomes, multinucleated cells, and multipolar spindles. Che-1 is required for Chk1 binding to pericentrin and centrosomal localization of Chk1, which regulates centrosomal cyclin B-Cdk1 activation and mitotic entry timing. Immunofluorescence localization, siRNA knockdown, co-immunoprecipitation (Chk1-pericentrin), flow cytometry, centrosome counting The Journal of biological chemistry High 23798705
2014 HIPK2 interacts with Che-1/AATF and phosphorylates it at specific residues upon genotoxic stress, strongly enhancing HDM2/Che-1 interaction and subsequent ubiquitin-mediated proteasomal degradation. HIPK2 depletion reduces Che-1 ubiquitylation and degradation; Che-1 overexpression counteracts HIPK2-induced apoptosis. Co-immunoprecipitation, in vitro kinase assay, ubiquitylation assay, siRNA knockdown, apoptosis assay Cell death & disease High 25210797
2015 Under stress conditions, Che-1/AATF inhibits mTOR activity by inducing expression of the mTOR inhibitors Redd1 and Deptor, and this activity is required for stress-induced autophagy. siRNA knockdown, gene expression analysis, Western blot, autophagy assays The EMBO journal Medium 25770584
2015 Che-1/AATF directly binds p53 protein, and this interaction occurs early in DNA damage response but is lost when cells undergo apoptosis. Che-1 forms a ternary complex with p53 and Brca1. Genome-wide ChIP analysis shows that Che-1/p53 interaction results in preferential transactivation of growth-arrest p53 target genes over pro-apoptotic targets. Che-1(+/-) mice show enhanced thymocyte apoptosis after ionizing radiation. Co-immunoprecipitation, genome-wide ChIP-seq, heterozygous knockout mouse model, irradiation assay Cell death & disease High 25996291
2016 AATF forms a salt-stable protein complex with neuroguidin (NGDN) and NOL10 (the ANN complex). All three members localize to nucleoli with mutual dependence for protein stability. The ANN complex is required for 18S rRNA maturation and nucleolar cleavage steps in the 5'ETS and ITS1 regions, supporting 40S ribosomal subunit biosynthesis. Immunoprecipitation (mass spectrometry), protein-protein interaction domain mapping, siRNA knockdown, rRNA processing analysis (Northern blot/pulse-chase), immunofluorescence Nucleic acids research High 27599843
2017 Che-1/AATF is required for HIF-1α stabilization under hypoxia; Che-1 depletion downregulates SIAH-2 expression (E3 ubiquitin ligase that degrades PHD3, the master regulator of HIF-1α stability), thereby reducing hypoxia-responsive gene expression and affecting glucose metabolism. siRNA knockdown, Western blot, NMR spectroscopy (metabolic), RNA-seq, ChIP Journal of experimental & clinical cancer research Medium 28214471
2018 In Kras-driven murine lung adenocarcinomas, AATF deletion delayed lung cancer formation predominantly in a p53-dependent manner, and targeting Aatf in existing tumors halted tumor progression. This identifies AATF as a key molecule sustaining proliferative tissue and tumor progression partly by inhibiting p53-driven apoptosis in vivo. Autochthonous Kras-driven mouse lung cancer model, dual recombinase conditional deletion, histology, survival analysis Oncogene High 29321668
2018 c-Myc directly binds the Che-1/AATF promoter to regulate its expression, and Che-1 acts as a downstream effector of c-Myc. Genome-wide ChIP-seq shows overlapping genomic occupancy; RNA-seq upon depletion of either protein reveals strong overlap of controlled pathways. Che-1 depletion inhibits BCP-ALL cell proliferation. ChIP-seq, RNA-seq, siRNA knockdown, promoter binding assay, proliferation assay EMBO reports High 29367285
2020 Che-1/AATF interacts with RNA polymerase I and the nucleolar upstream binding factor UBF, promotes RNA polymerase I-dependent transcription of rRNA genes (rDNA), and binds the rDNA promoter. Che-1 depletion reduces RNA Pol I and UBF recruitment on rDNA, decreases rDNA promoter activity and 47S pre-rRNA production, and induces abnormal nucleolar morphology. Upon DNA damage, Che-1 re-localizes from rDNA to the TP53 promoter. Co-immunoprecipitation (RNA Pol I, UBF), ChIP, reporter assay, siRNA knockdown, pre-rRNA Northern blot, immunofluorescence Nucleic acids research High 32421830
2020 Che-1/AATF directly interacts with histones and displaces HDAC class I members from histones in multiple myeloma cells, promoting global histone acetylation and active chromatin. Che-1 depletion leads to global histone deacetylation and reduced BRD4 chromatin accumulation. Transgenic mice expressing human Che-1 in plasma cells develop multiple myeloma. Co-immunoprecipitation (histones), HDAC displacement assay, ChIP-seq, Western blot, transgenic mouse model Blood advances High 33186461
2021 CK2 protein kinase phosphorylates Che-1/AATF at Ser316, Ser320, and Ser321. These phosphorylation events are required for Che-1/histone H3 interaction and for Che-1's pro-proliferative activity. Mutation of these serines (Che-1 3S mutant) abolishes histone H3 binding. In vitro kinase assay (CK2), site-directed mutagenesis, 2D gel electrophoresis, mass spectrometry, co-immunoprecipitation, proliferation assay Journal of experimental & clinical cancer research High 34266450
2022 AATF/Che-1 localizes to paraspeckles via interaction with the lncRNA NEAT1_2 and directly localizes on R-loops. Depletion of Che-1 causes marked accumulation of RNA:DNA hybrids (R-loops) and triggers sustained interferon gene expression signature through failure to resolve R-loops. Immunoprecipitation (NEAT1 lncRNA interaction), R-loop immunofluorescence/dot blot (S9.6 antibody), siRNA knockdown, RNA-seq (IFN signature), ChIP The EMBO journal High 35929179
2022 In ischemic neurons, AATF competitively interacts with nuclear apoptosis-inducing factor (AIF) and inhibits AIF from binding DNA, thereby suppressing parthanatos (AIF-mediated cell death) without affecting PAR accumulation or AIF nuclear translocation. Co-immunoprecipitation (AATF-AIF), OGD/R model, dMCAO/R in vivo model, DNA fragmentation assay, overexpression Journal of molecular neuroscience Medium 36058992
2023 HAX1 is a novel binding partner of Che-1/AATF; both proteins colocalize extensively in mitochondria and their association is strengthened after oxidative stress. Che-1 depletion correlates with decreased HAX1 mRNA and protein levels in MCF-7 cells. Co-immunoprecipitation, co-localization (immunofluorescence), siRNA knockdown, Western blot Biochimica et biophysica acta. Molecular cell research Low 37742722
2025 AATF interacts with XRCC4 (a core NHEJ subunit) and prevents its ubiquitin-mediated proteasomal degradation. Upon DNA damage, ATM phosphorylates AATF at Ser189, causing its dissociation from XRCC4 and rapid recruitment of XRCC4 to DNA break sites for NHEJ repair. AATF depletion or phosphorylation-deficient mutant impedes NHEJ in glioma stem-like cells. Co-immunoprecipitation (AATF-XRCC4), ATM kinase assay (Ser189 phosphorylation), site-directed mutagenesis, NHEJ assay, ubiquitination assay, xenograft model Nature communications High 40436899
2017 Che-1/AATF interacts with subunits of the HAT module of SAGA complexes (ADA2A, ADA2B, and GCN5) in human cells, as demonstrated by co-immunoprecipitation and co-localization, with specific domains in ADA2 and GCN5 required for these interactions. Co-immunoprecipitation, yeast two-hybrid (domain mapping), co-localization PloS one Medium 29232376
2003 The Che-1/AATF promoter is TATA-less and contains a negative feedback element: Che-1 protein binds its own promoter and represses its own transcription. Reporter assay, chromatin immunoprecipitation (ChIP), promoter deletion analysis Gene Medium 14636992
2025 In pancreatic neuroendocrine tumors, ACSS2 activity induces histone H3/H4 hyperacetylation, which recruits AATF to co-regulate FasL transcription, specifically enhancing soluble FasL secretion. Secreted FasL triggers CD8+ T cell apoptosis via caspase-8/3 cascade, promoting immune evasion. ACSS2 and AATF act non-redundantly and synergistically in modulating FasL expression. ChIP, Western blot, ELISA (sFasL), co-immunoprecipitation, siRNA/overexpression, flow cytometry (T cell apoptosis) Advanced science Medium 40791180

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Cell death and differentiation 262 10200473
2016 Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex. Molecular cell 153 27746017
2003 The C. elegans che-1 gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons. Development (Cambridge, England) 140 12588839
2006 Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer cell 112 17157788
2000 Identification of a novel partner of RNA polymerase II subunit 11, Che-1, which interacts with and affects the growth suppression function of Rb. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 75 10783144
1999 AATF, a novel transcription factor that interacts with Dlk/ZIP kinase and interferes with apoptosis. FEBS letters 74 10580117
2015 Molecular architecture of the DED chains at the DISC: regulation of procaspase-8 activation by short DED proteins c-FLIP and procaspase-8 prodomain. Cell death and differentiation 71 26494467
2014 Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly. Nature communications 70 24577104
2002 Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb. Cancer cell 67 12450794
2015 Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy. The EMBO journal 58 25770584
2009 AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional regulation of AKT1. Cell death and differentiation 56 19911006
2020 Controlling Cell Death through Post-translational Modifications of DED Proteins. Trends in cell biology 53 32302548
2007 NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. Journal of cell science 53 17488777
2012 AATF/Che-1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis. The EMBO journal 51 22909821
2014 Crystal structure of the F27G AIM2 PYD mutant and similarities of its self-association to DED/DED interactions. Journal of molecular biology 48 24406744
2015 DED or alive: assembly and regulation of the death effector domain complexes. Cell death & disease 47 26313917
2003 AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4. The Journal of biological chemistry 43 14627703
2015 Discovering Che-1/AATF: a new attractive target for cancer therapy. Frontiers in genetics 42 25914721
2003 Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter. The Journal of biological chemistry 42 12847090
2010 Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation. Cancer cell 41 20708154
2007 The prolyl isomerase Pin1 affects Che-1 stability in response to apoptotic DNA damage. The Journal of biological chemistry 41 17468107
2010 Molluscan death effector domain (DED)-containing caspase-8 gene from disk abalone (Haliotis discus discus): molecular characterization and expression analysis. Fish & shellfish immunology 35 21130887
2007 Che-1 activates XIAP expression in response to DNA damage. Cell death and differentiation 35 18049476
2023 [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data. Journal of neuroinflammation 34 36906584
2015 Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53. Cell death & disease 34 25996291
2021 Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments. Experimental eye research 31 34384756
2006 Functional characterization of AATF transcriptome in human leukemic cells. Molecular and cellular biochemistry 30 17006618
2019 Long and short isoforms of c-FLIP act as control checkpoints of DED filament assembly. Oncogene 29 31740779
2003 Homology modeling provides insights into the binding mode of the PAAD/DAPIN/pyrin domain, a fourth member of the CARD/DD/DED domain family. Protein science : a publication of the Protein Society 29 12930987
2003 Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons. Modulation during neuronal apoptosis. Molecular and cellular neurosciences 27 14697667
2007 The anti-apoptotic factor Che-1/AATF links transcriptional regulation, cell cycle control, and DNA damage response. Cell division 26 17634135
2018 AATF suppresses apoptosis, promotes proliferation and is critical for Kras-driven lung cancer. Oncogene 25 29321668
2017 Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization. Journal of experimental & clinical cancer research : CR 25 28214471
2024 Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis. Nature communications 24 38710704
2007 Che-1/AATF, a multivalent adaptor connecting transcriptional regulation, checkpoint control, and apoptosis. Biochemistry and cell biology = Biochimie et biologie cellulaire 24 17713582
2004 AATF protects neural cells against oxidative damage induced by amyloid beta-peptide. Neurobiology of disease 24 15207272
2018 Che-1 is targeted by c-Myc to sustain proliferation in pre-B-cell acute lymphoblastic leukemia. EMBO reports 23 29367285
2016 Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis. Nucleic acids research 23 27599843
2013 Nucleolar proteins Bfr2 and Enp2 interact with DEAD-box RNA helicase Dbp4 in two different complexes. Nucleic acids research 23 24357410
2012 Nucleolar AATF regulates c-Jun-mediated apoptosis. Molecular biology of the cell 23 22933572
2022 DED Interaction of FADD and Caspase-8 in the Induction of Apoptotic Cell Death. Journal of microbiology and biotechnology 22 35879276
2016 A distinct cytokines profile in tear film of dry eye disease (DED) patients with HIV infection. Cytokine 20 27585367
2013 Apoptosis-antagonizing transcription factor (AATF) gene silencing: role in induction of apoptosis and down-regulation of estrogen receptor in breast cancer cells. Biotechnology letters 20 23801113
2022 AATF/Che-1 localizes to paraspeckles and suppresses R-loops accumulation and interferon activation in Multiple Myeloma. The EMBO journal 18 35929179
2020 Emerging roles of AATF: Checkpoint signaling and beyond. Journal of cellular physiology 18 33145763
2011 Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage. DNA repair 18 21317046
2020 Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription. Nucleic acids research 17 32421830
2016 Che-1/AATF: A Critical Cofactor for Both Wild-Type- and Mutant-p53 Proteins. Frontiers in oncology 17 26913241
2016 eEF1Bγ binds the Che-1 and TP53 gene promoters and their transcripts. Journal of experimental & clinical cancer research : CR 17 27639846
2013 Centrosomal Che-1 protein is involved in the regulation of mitosis and DNA damage response by mediating pericentrin (PCNT)-dependent Chk1 protein localization. The Journal of biological chemistry 16 23798705
2015 Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three-Dimensional Structure, Immune Activation, and Involvement in Dry Eye Disease (DED). Investigative ophthalmology & visual science 15 26559477
2020 AATF and SMARCA2 are associated with thyroid volume in Hashimoto's thyroiditis patients. Scientific reports 13 32019955
2014 HIPK2 sustains apoptotic response by phosphorylating Che-1/AATF and promoting its degradation. Cell death & disease 13 25210797
2020 Che-1/AATF-induced transcriptionally active chromatin promotes cell proliferation in multiple myeloma. Blood advances 12 33186461
2018 Che-1 attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by upregulation of Nrf2 signaling. European review for medical and pharmacological sciences 12 29509260
2003 Genomic structure and transcriptional regulation of Che-1, a novel partner of Rb. Gene 12 14636992
2023 AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma. Frontiers in oncology 11 37361585
2022 Comparison of Trehalose/Hyaluronic Acid (HA) vs. 0.001% Hydrocortisone/HA Eyedrops on Signs and Inflammatory Markers in a Desiccating Model of Dry Eye Disease (DED). Journal of clinical medicine 11 35329844
2007 Characterization of rat BLOS2/Ceap, a putative yeast She3 homolog, as interaction partner of apoptosis antagonizing transcription factor/Che-1. Biological chemistry 11 17552904
1998 Multidrug resistance phenotype conferred by overexpressing bfr2+/pad1+/sks1+ or pap1+ genes and mediated by bfr1+ gene product, a structural and functional homologue of P-glycoprotein in Schizosaccharomyces pombe. Bioscience, biotechnology, and biochemistry 11 9532803
2024 BFR2: a curated ribosomal reference dataset for benthic foraminifera. Scientific data 10 39604449
2022 Tear film instability is associated with weakened colocalization between occludin and MUC5AC in scopolamine-induced dry eye disease (DED) rats. International ophthalmology 10 35908134
2020 AATF/Che-1-An RNA Binding Protein at the Nexus of DNA Damage Response and Ribosome Biogenesis. Frontiers in oncology 10 32587828
2009 Novel activation domain derived from Che-1 cofactor coupled with the artificial protein Jazz drives utrophin upregulation. Neuromuscular disorders : NMD 10 19162479
2009 Mutation analysis of the AATF gene in breast cancer families. BMC cancer 10 20025740
2024 Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes. Nature communications 9 39419969
2018 The PI3K/AKT axis modulates AATF activity in Wilms' tumor cells. FEBS open bio 9 30338213
2009 Cellular AATF gene encodes a novel miRNA that can contribute to HIV-1 latency. Indian journal of biochemistry & biophysics 9 27804285
2006 DNA damage signaling recruits the RNA polymerase II binding protein Che-1 to the p53 promoter. Molecular cell 9 17189183
2025 Elevated nonhomologous end-joining by AATF enables efficient DNA damage repair and therapeutic resistance in glioblastoma. Nature communications 8 40436899
2023 Modified Danzhi Xiaoyao Powder (MDXP) improves the corneal damage in dry eye disease (DED) mice through phagocytosis. Journal of ethnopharmacology 8 38070838
2020 Osteo-Compatibility of 3D Titanium Porous Coating Applied by Direct Energy Deposition (DED) for a Cementless Total Knee Arthroplasty Implant: in Vitro and in Vivo Study. Journal of clinical medicine 8 32050490
2012 Targeting BCR tyrosine177 site with novel SH2-DED causes selective leukemia cell death in vitro and in vivo. The international journal of biochemistry & cell biology 8 22349215
1998 Expression of the yeast BFR2 gene is regulated at the transcriptional level and through degradation of its product. Molecular & general genetics : MGG 8 9645427
2021 The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2. Viruses 7 34202565
2021 AATF is Overexpressed in Human Head and Neck Squamous Cell Carcinoma and Regulates STAT3/Survivin Signaling. OncoTargets and therapy 7 34785906
2020 Titanium Porous Coating Using 3D Direct Energy Deposition (DED) Printing for Cementless TKA Implants: Does It Induce Chronic Inflammation? Materials (Basel, Switzerland) 7 31963803
2018 Che-1 inhibits oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis associated with inhibition of the p53-mediated proapoptotic signaling pathway. Neuroreport 7 30001227
2016 Che-1 gene silencing induces osteosarcoma cell apoptosis by inhibiting mutant p53 expression. Biochemical and biophysical research communications 7 27012205
2024 Targeting type I DED interactions at the DED filament serves as a sensitive switch for cell fate decisions. Cell chemical biology 6 39053461
2024 TACE inhibition: a promising therapeutic intervention against AATF-mediated steatohepatitis to hepatocarcinogenesis. Molecular oncology 5 38558505
2021 CK2-mediated phosphorylation of Che-1/AATF is required for its pro-proliferative activity. Journal of experimental & clinical cancer research : CR 5 34266450
2017 Che1/AATF interacts with subunits of the histone acetyltransferase core module of SAGA complexes. PloS one 5 29232376
2016 APOBEC3G governs the generation of truncated AATF protein to ensure oncogenic transformation. Cell biology international 5 27611213
2007 Cellular AATF gene: armour against HIV-1. Indian journal of biochemistry & biophysics 5 18341201
2025 FADDDED filaments coordinate complex IIa assembly during TNF-induced apoptosis. Proceedings of the National Academy of Sciences of the United States of America 4 40838879
2023 MitomiR-1736-3p regulates copper-induced mitochondrial pathway apoptosis by inhibiting AATF in chicken hepatocytes. The Science of the total environment 4 37839473
2022 Artificial intelligence-assisted cryoEM structure of Bfr2-Lcp5 complex observed in the yeast small subunit processome. Communications biology 4 35650250
2022 AATF Competitively Interacts with Nuclear AIF and Inhibits Parthanatos of Neurons in dMCAO/R and OGD/R Models. Journal of molecular neuroscience : MN 4 36058992
2020 Mathematical Modeling Reveals the Importance of the DED Filament Composition in the Effects of Small Molecules Targeting Caspase-8/c-FLIPL Heterodimer. Biochemistry. Biokhimiia 4 33202199
2012 Che-ating death: CHE1/AATF protects from p53-mediated apoptosis. The EMBO journal 4 22960635
2005 DED: Database of Evolutionary Distances. Nucleic acids research 4 15608234
2025 ACSS2/AATF Drives Soluble FasL-Mediated CD8+ T Cell Apoptosis in Pancreatic Neuroendocrine Tumors. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40791180
2021 AATF is Overexpressed in Human Bladder Cancer and Regulates Chemo-Sensitivity Through Survivin. OncoTargets and therapy 3 35002255
2012 Up-regulation of Che-1 relates to neuronal apoptosis after traumatic brain injury in adult rats. Cellular and molecular neurobiology 3 23007641
2008 Che-1 enhances cyclin-dependent kinase 5 expression and interacts with the active kinase-complex. Neuroreport 3 18388733
2007 Che-1: a new effector of checkpoints signaling. Cell cycle (Georgetown, Tex.) 3 17377493
1998 Over-expression of the yeast BFR2 gene partially suppresses the growth defects induced by Brefeldin A and by four ER-to-Golgi mutations. Current genetics 3 9472076
2023 HAX1 is a novel binding partner of Che-1/AATF. Implications in oxidative stress cell response. Biochimica et biophysica acta. Molecular cell research 2 37742722
2018 A new baby in the c-Myc-directed transcriptional machinery: Che-1/AATF. Cell cycle (Georgetown, Tex.) 2 29943642

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