Affinage

AATF

Protein AATF · UniProt Q9NY61

Length
560 aa
Mass
63.1 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AATF/Che-1 is a multifunctional nuclear and nucleolar protein that integrates transcriptional regulation, ribosome biogenesis, DNA repair, and R-loop resolution to govern cell proliferation and stress responses. It binds RNA polymerase II, retinoblastoma protein (Rb), and histones, displacing HDAC1 from Rb/E2F complexes, Sp1-containing promoters, and chromatin to activate E2F-dependent proliferation, p21-mediated growth arrest, and global histone acetylation (PMID:12450794, PMID:12847090, PMID:33186461). Upon genotoxic stress, AATF is phosphorylated by ATM/ATR/Chk2, MK2, and CK2, which drive its nuclear translocation, stabilization, and selective recruitment to p53/p21 promoters while repressing pro-apoptotic targets (PUMA, BAX, BAK), and ATM-mediated Ser189 phosphorylation releases AATF from XRCC4 to enable NHEJ repair (PMID:17157788, PMID:22909821, PMID:40436899). As a core subunit of the ANN complex (with NGDN and NOL10), AATF binds 45S pre-rRNA near SSU cleavage sites and interacts with RNA polymerase I/UBF to promote 18S rRNA maturation and 40S ribosomal subunit biogenesis, and it localizes to paraspeckles via NEAT1 lncRNA to resolve R-loops and suppress interferon signaling (PMID:27599843, PMID:31363146, PMID:32421830, PMID:35929179).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 Medium

    Establishing AATF as a nuclear phosphoprotein with transactivation capacity that antagonizes kinase-induced apoptosis resolved the initial identity of the gene product and its anti-apoptotic orientation.

    Evidence Yeast two-hybrid identification of Dlk/ZIP kinase interaction, Gal4 transactivation assay, and apoptosis interference assay

    PMID:10580117

    Open questions at the time
    • Dlk interaction validated only by yeast two-hybrid with overexpression follow-up
    • endogenous relevance of Dlk–AATF axis unresolved
    • mechanism of apoptosis inhibition undefined
  2. 2000 Medium

    Demonstrating that AATF/Che-1 binds both RNA polymerase II (via hRPB11) and Rb established it as a transcriptional cofactor that modulates Rb-mediated growth suppression and E2F1 transactivation.

    Evidence Co-immunoprecipitation, two-hybrid, and transactivation rescue assays

    PMID:10783144

    Open questions at the time
    • Rb interaction domains mapped but stoichiometry and in vivo relevance not established
    • no genome-wide target identification
  3. 2002 High

    Showing that Che-1 competes with HDAC1 for the Rb pocket and is recruited to E2F target promoters resolved the mechanism by which AATF promotes cell cycle entry — through derepression of E2F targets via HDAC1 displacement.

    Evidence In vitro binding competition, ChIP at E2F promoters, RNAi in pocket-protein-competent cells, cell cycle assay

    PMID:12450794

    Open questions at the time
    • Whether HDAC1 displacement is the sole mechanism for E2F activation
    • contribution of other pocket proteins (p107, p130) not dissected
  4. 2003 High

    Extending the HDAC1-displacement mechanism to the p21 promoter via Sp1 showed that AATF drives growth arrest as well as proliferation depending on promoter context, revealing context-dependent transcriptional outcomes.

    Evidence ChIP at Sp1 sites on p21 promoter, RNAi, histone acetylation analysis, cell cycle assay in colon carcinoma cells

    PMID:12847090

    Open questions at the time
    • How AATF is directed to proliferative versus growth-arrest promoters is unclear
    • Sp1/HDAC1 competition not reconstituted with purified components
  5. 2003 Medium

    Identification of Par-4 and Tau as AATF-binding partners in neural cells broadened the functional scope of AATF beyond cell cycle control to neuronal apoptosis regulation and Aβ production.

    Evidence Co-immunoprecipitation, FRET (for Tau), colocalization, Aβ ELISA (for Par-4) in cerebellar granule neurons and neural cell lines

    PMID:14627703 PMID:14697667

    Open questions at the time
    • Physiological relevance in neurodegeneration models not tested
    • downstream signaling mechanisms linking AATF-Par-4 to Aβ production undefined
  6. 2006 High

    Discovery that ATM/ATR and Chk2 phosphorylate and stabilize Che-1 upon DNA damage, recruiting it to the p53 and p21 promoters, placed AATF squarely in the DNA damage checkpoint signaling cascade and explained its damage-induced stabilization.

    Evidence Kinase assay, co-immunoprecipitation with ATM/ATR/Chk2, ChIP at p53 promoter, siRNA, G2/M checkpoint analysis

    PMID:17157788

    Open questions at the time
    • Specific phosphorylation sites mediating each functional outcome not fully mapped
    • relative contributions of ATM versus ATR not separated
  7. 2007 High

    Elucidation of the Pin1/HDM2-dependent degradation pathway showed how apoptotic signals eliminate AATF's anti-apoptotic function, establishing that the balance between kinase-mediated stabilization and Pin1/HDM2-dependent turnover dictates cell fate.

    Evidence Co-immunoprecipitation, ubiquitination assay, protein stability assay, Pin1-binding-deficient mutagenesis

    PMID:17468107

    Open questions at the time
    • Identity of the proline-directed kinase priming Pin1 binding unclear
    • whether this pathway operates in all cell types not addressed
  8. 2009 High

    Positioning AATF downstream of the PERK–eIF2α UPR branch as a transcriptional activator of AKT1 via STAT3 revealed a new stress-responsive axis extending AATF's survival function beyond DNA damage to ER stress.

    Evidence Gene expression profiling, RNAi epistasis (PERK→AATF→STAT3→AKT1), ER stress cell death assay

    PMID:19911006

    Open questions at the time
    • Direct binding of AATF to AKT1 promoter not shown by ChIP in this study
    • mechanism of PERK/eIF2α-mediated AATF induction not delineated
  9. 2011 High

    Identification of PARP-1-mediated PARylation as an ATM-independent stabilization mechanism for Che-1 added a second post-translational axis controlling AATF protein levels and its promoter occupancy at p21.

    Evidence In vitro PARylation assay, PARP-1 knockout cells, PARP inhibition, ChIP at p21 promoter

    PMID:21317046

    Open questions at the time
    • Sites of PARylation on AATF not mapped
    • interplay between PARylation and phosphorylation not resolved
  10. 2012 High

    Demonstration that MK2 phosphorylates AATF to release it from cytoplasmic MRLC3, enabling nuclear entry and selective repression of pro-apoptotic p53 targets (PUMA, BAX, BAK), resolved how genotoxic stress channels AATF toward anti-apoptotic gene regulation.

    Evidence Kinase assay, subcellular fractionation, ChIP at PUMA/BAX/BAK promoters, phospho-mimicking mutagenesis, xenograft model

    PMID:22909821

    Open questions at the time
    • Mechanism of selective repression of pro-apoptotic versus growth-arrest promoters not fully explained
    • MRLC3 sequestration mechanism not structurally characterized
  11. 2014 High

    Showing that HIPK2 phosphorylation promotes HDM2-mediated ubiquitination and degradation of Che-1 identified the upstream kinase that primes the degradation switch, complementing the earlier Pin1/HDM2 pathway and establishing a pro-apoptotic kinase–AATF antagonism.

    Evidence Kinase assay, ubiquitination assay, siRNA of HIPK2, apoptosis rescue by Che-1 overexpression

    PMID:25210797

    Open questions at the time
    • Relationship between HIPK2 and Pin1 in sequential modification not tested
    • specific HIPK2 phosphosites and their individual contributions not fully resolved
  12. 2015 High

    ChIP-seq demonstration that Che-1 forms a ternary complex with p53 and BRCA1 to preferentially activate growth-arrest over pro-apoptotic p53 targets, validated in Che-1+/− mice, provided genome-wide evidence for how AATF biases p53 output toward survival.

    Evidence ChIP-seq, co-immunoprecipitation, heterozygous mouse model with ionizing radiation challenge

    PMID:25996291

    Open questions at the time
    • BRCA1's structural role in the ternary complex undefined
    • complete null mouse phenotype not reported
  13. 2016 High

    Identification of the ANN complex (AATF–NGDN–NOL10) and its requirement for 18S rRNA maturation established AATF as a core component of small ribosomal subunit biogenesis, revealing a function independent of its transcriptional activities.

    Evidence Immunoprecipitation, domain mapping, siRNA depletion of each component, northern blot rRNA processing assay, nucleolar localization

    PMID:27599843

    Open questions at the time
    • Enzymatic activity within the ANN complex not identified
    • whether ANN complex function is linked to AATF's stress-responsive roles unknown
  14. 2019 High

    CLIP-seq mapping of AATF RNA-binding sites to 45S pre-rRNA near SSU cleavage regions, combined with a comprehensive mass spectrometry interactome, confirmed direct RNA engagement and connected AATF to a broad rRNA maturation protein network.

    Evidence CLIP-seq, mass spectrometry interactome analysis

    PMID:31363146

    Open questions at the time
    • Structure of AATF–pre-rRNA complex not determined
    • RNA-binding domain not delineated
  15. 2020 High

    Showing that Che-1 occupies the rDNA promoter, interacts with RNA Pol I and UBF, and dynamically relocalizes from rDNA to the p53 promoter upon DNA damage unified AATF's ribosome biogenesis and DNA damage transcription functions as a nucleolar stress sensor.

    Evidence ChIP at rDNA promoter, co-immunoprecipitation with Pol I/UBF, rRNA synthesis assay, damage-induced relocalization

    PMID:32421830

    Open questions at the time
    • Signal triggering relocalization from rDNA to p53 promoter not identified
    • whether Pol I interaction requires the ANN complex unclear
  16. 2020 High

    Demonstration that Che-1 directly binds histones, displaces class I HDACs globally, and sustains histone acetylation — with transgenic Che-1 mice developing multiple myeloma — extended the HDAC-displacement mechanism from promoter-specific to genome-wide and established oncogenic potential in plasma cells.

    Evidence Co-immunoprecipitation with histones, histone acetylation assay, transgenic mouse model, siRNA

    PMID:33186461

    Open questions at the time
    • Specificity of histone mark changes not profiled genome-wide
    • whether CK2 phosphorylation is required for histone binding in vivo not tested in this study
  17. 2021 High

    Identification of CK2 as a kinase phosphorylating Che-1 at Ser316/320/321 to enable histone H3 binding provided the post-translational mechanism controlling AATF's HDAC-displacement and proliferative activity.

    Evidence In vitro kinase assay, site-directed mutagenesis, mass spectrometry, co-immunoprecipitation with histone H3, proliferation assay

    PMID:34266450

    Open questions at the time
    • Whether CK2 phosphorylation intersects with ATM/MK2 phosphorylation cascades unknown
    • structural basis for phospho-dependent histone binding not resolved
  18. 2022 High

    Discovery that AATF localizes to paraspeckles via NEAT1 lncRNA and directly resolves R-loops, with its depletion triggering interferon gene activation, revealed a novel genome-integrity function connecting AATF to innate immune suppression.

    Evidence NEAT1 co-immunoprecipitation, S9.6 R-loop immunoprecipitation, RNA-seq, siRNA, paraspeckle imaging

    PMID:35929179

    Open questions at the time
    • Enzymatic or catalytic mechanism of R-loop resolution by AATF not identified
    • whether R-loop function depends on the ANN complex or other partners unknown
  19. 2025 High

    Establishing that AATF protects XRCC4 from ubiquitin-mediated degradation and that ATM-mediated Ser189 phosphorylation releases AATF from XRCC4 to permit NHEJ defined a direct DNA repair function and a damage-responsive switch with therapeutic relevance in glioblastoma.

    Evidence Co-immunoprecipitation, mass spectrometry, in vitro ATM phosphorylation assay, Ser189 mutagenesis, NHEJ reporter assay, glioblastoma xenograft model

    PMID:40436899

    Open questions at the time
    • Whether AATF also affects alternative end-joining or homologous recombination
    • structural basis of AATF–XRCC4 interaction unknown
    • relationship between Ser189 phosphorylation and other ATM-dependent AATF phosphorylation events not clarified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of AATF's RNA-binding and histone-binding activities, how AATF is coordinately regulated by its multiple kinase inputs (ATM, MK2, CK2, HIPK2) to select between transcriptional programs, and whether its ribosome biogenesis, R-loop resolution, and NHEJ functions are mechanistically interconnected.
  • No high-resolution structure of AATF or its complexes available
  • integrated signaling model for multi-kinase regulation lacking
  • functional hierarchy among ribosome biogenesis, R-loop resolution, and NHEJ roles not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 2 GO:0003723 RNA binding 2 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 6 GO:0005730 nucleolus 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-5357801 Programmed Cell Death 5 R-HSA-1640170 Cell Cycle 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 1
Partners
BRCA1HDAC1NEAT1NGDNNOL10RB1TP53XRCC4
Complex memberships
ANN complex (AATF–NGDN–NOL10)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 AATF (apoptosis antagonizing transcription factor) was identified as a nuclear phosphoprotein that interacts with Dlk/ZIP kinase (a serine/threonine kinase) and interferes with Dlk-induced apoptosis. AATF contains an acidic domain and a leucine zipper, and a Gal4-BD-AATF fusion protein exhibited strong transactivation activity. Yeast two-hybrid screen, transactivation assay, apoptosis interference assay FEBS letters Medium 10580117
2000 AATF/Che-1 interacts with hRPB11 (a core subunit of RNA polymerase II) and also binds the retinoblastoma protein (Rb) via two distinct domains, repressing Rb-mediated growth suppression and counteracting Rb inhibition of E2F1 transactivation. Co-immunoprecipitation, two-hybrid, transactivation assay, domain mapping 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 the Rb/E2F complex in vitro and from E2F target promoters in vivo, thereby activating DNA synthesis in quiescent cells. Che-1-specific RNAi confirmed its requirement in pocket protein-competent cells. Co-immunoprecipitation, ChIP, RNA interference, in vitro binding competition, cell cycle assay Cancer cell High 12450794
2003 Che-1/AATF activates p21WAF1/CIP1 expression by displacing HDAC1 from Sp1 binding sites on the p21 promoter, leading to accumulation of acetylated histone H3 and G1 growth arrest in colon carcinoma cells. ChIP, RNA interference, overexpression, cell cycle analysis The Journal of biological chemistry High 12847090
2003 AATF directly interacts with Par-4 (prostate apoptosis response-4) via the leucine zipper domain in neural cells, colocalizing in both cytoplasmic and nuclear compartments. This AATF/Par-4 complex formation is essential for AATF's inhibitory effect on aberrant Aβ-(1-42) production and secretion induced by Par-4. Co-immunoprecipitation, colocalization, overexpression, Aβ ELISA The Journal of biological chemistry Medium 14627703
2003 Che-1/AATF directly interacts with Tau protein in cerebellar granule neurons (CGNs), binding the amino-terminal region of Tau. This interaction is modulated during neuronal apoptosis and was confirmed by co-immunoprecipitation and FRET analysis. Co-immunoprecipitation, FRET, overexpression Molecular and cellular neurosciences Medium 14697667
2003 Che-1/AATF expression is regulated by a negative autoregulatory feedback loop in which the protein binds its own promoter and represses transcription. ChIP, promoter reporter assay Gene Medium 14636992
2006 ATM/ATR and Chk2 checkpoint kinases physically interact with Che-1/AATF and phosphorylate it in response to DNA damage, promoting its accumulation and stabilization. These modifications induce recruitment of Che-1 to the TP53 and p21 promoters, activating p53 expression and contributing to maintenance of the G2/M checkpoint. Co-immunoprecipitation, ChIP, kinase assay, siRNA, cell cycle analysis Cancer cell High 17157788
2007 In response to apoptotic stimuli, Che-1/AATF interacts with the prolyl isomerase Pin1, and this interaction causes conformational changes that promote Che-1 interaction with the E3 ubiquitin ligase HDM2, leading to ubiquitin-dependent proteasomal degradation of Che-1. A Pin1-binding-deficient Che-1 mutant had an increased half-life and reduced apoptosis. Co-immunoprecipitation, protein stability assay, site-directed mutagenesis, ubiquitination assay The Journal of biological chemistry High 17468107
2007 NRAGE interacts with Che-1/AATF and inhibits its nuclear localization by sequestering it in the cytoplasmic compartment. NRAGE overexpression targets Che-1 for proteasome-dependent degradation. Overexpression of Che-1 completely reverses NRAGE-induced cell death. Co-immunoprecipitation, live-cell imaging (EGFP fusion), proteasome inhibitor assay, apoptosis assay Journal of cell science Medium 17488777
2007 Che-1/AATF activates XIAP expression in response to DNA damage through a mechanism requiring Che-1 phosphorylation and NF-κB. XIAP expression was found necessary for the anti-apoptotic activity of Che-1. siRNA, reporter assay, western blot, in vivo xenograft Cell death and differentiation Medium 18049476
2009 AATF mediates an anti-apoptotic effect of the unfolded protein response (UPR) by being induced through the PERK-eIF2α pathway during ER stress. AATF then transcriptionally activates AKT1 through STAT3, sustaining Akt1 activation and promoting cell survival. RNAi knockdown of AATF or AKT1 sensitized cells to ER stress-mediated cell death. Gene expression profiling, RNAi, reporter assay, western blot, ER stress cell death assay Cell death and differentiation High 19911006
2011 PARP-1 directly interacts with Che-1/AATF and promotes its poly(ADP-ribosyl)ation both in vitro and in vivo. This modification is required for Che-1 stabilization following DNA damage, acting independently of ATM kinase activity and controlling Che-1 occupancy at the p21 promoter. Co-immunoprecipitation, in vitro PARylation assay, PARP inhibition, PARP-1 knockout, ChIP DNA repair High 21317046
2012 Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. This phosphorylation causes release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation, where AATF binds PUMA, BAX, and BAK promoters to repress p53-driven expression of pro-apoptotic genes. A phospho-mimicking AATF mutant conferred adriamycin resistance in vivo. Kinase assay, subcellular fractionation, ChIP, site-directed mutagenesis, xenograft model The EMBO journal High 22909821
2012 AATF is a nucleolar stress sensor that translocates from the nucleolus to the nucleus upon UV irradiation, physically associating with c-Jun to act as a cofactor for c-Jun-mediated transcription of pro-apoptotic genes (FasL, TNF-α). AATF mutants defective in c-Jun binding failed to induce AP-1 activity or c-Jun-dependent apoptosis. Co-immunoprecipitation, subcellular localization imaging, reporter assay, domain deletion mutagenesis, c-Jun-deficient MEFs Molecular biology of the cell High 22933572
2013 Che-1/AATF localizes at interphase centrosomes in addition to its nuclear localization, accumulating there following DNA damage or spindle poisons. Che-1 depletion generates supernumerary centrosomes, multinucleated cells, and multipolar spindles. Mechanistically, Che-1 depletion abolishes Chk1 binding to pericentrin and its localization at centrosomes, deregulating centrosomal cyclin B-Cdk1 activation and advancing mitotic entry. Immunofluorescence localization, siRNA, centrosome counting, western blot, spindle checkpoint assay The Journal of biological chemistry Medium 23798705
2014 HIPK2 interacts with Che-1/AATF and phosphorylates it at specific residues upon genotoxic stress, which strongly increases HDM2/Che-1 interaction and Che-1 degradation via ubiquitin-dependent proteasomal system. HIPK2 depletion decreased Che-1 ubiquitylation and degradation, and Che-1 overexpression counteracted HIPK2-induced apoptosis. Co-immunoprecipitation, kinase assay, ubiquitination assay, siRNA, apoptosis assay Cell death & disease High 25210797
2015 Che-1/AATF directly binds p53 protein, and this interaction occurs preferentially in a ternary complex with Brca1 in the early hours of DNA damage. Genome-wide ChIP analysis revealed that Che-1/p53 interaction results in preferential transactivation of growth-arrest p53 target genes over pro-apoptotic targets. Che-1+/- mice showed enhanced thymocyte apoptosis after ionizing radiation. Co-immunoprecipitation, ChIP-seq, genome-wide chromatin occupancy, heterozygous mouse model Cell death & disease High 25996291
2015 Under stress conditions (nutrient limitation, hypoxia, DNA damage), Che-1/AATF inhibits mTOR activity by inducing expression of the mTOR inhibitors Redd1 and Deptor, and this activity is required for sustaining stress-induced autophagy. siRNA, western blot, autophagy assay, qRT-PCR, mTOR activity assay The EMBO journal Medium 25770584
2016 AATF forms a salt-stable protein complex with neuroguidin (NGDN) and NOL10 (the ANN complex). All three ANN complex members localize to nucleoli with mutual dependence for protein stability. The ANN complex supports nucleolar steps of 40S ribosomal subunit biosynthesis, being required for 18S rRNA maturation and specific nucleolar cleavage steps in the 5'ETS and ITS1 regions. Immunoprecipitation, domain mapping, siRNA depletion, rRNA processing assay, northern blot, nucleolar localization Nucleic acids research High 27599843
2017 Che-1/AATF interacts with subunits of the HAT module of SAGA complexes (ADA2A, ADA2B, and GCN5), as demonstrated by co-immunoprecipitation and yeast two-hybrid with domain delineation. Co-immunoprecipitation, yeast two-hybrid, colocalization PloS one Medium 29232376
2018 In Kras-driven murine lung adenocarcinomas, AATF/Che-1 is required to sustain tumor progression predominantly in a p53-dependent manner. In an autochthonous model, Aatf deletion delayed lung cancer formation, and targeting Aatf in existing tumors halted tumor progression, establishing AATF as a key suppressor of p53-driven apoptosis in vivo. Conditional knockout mouse, dual recombinase strategy, lung adenocarcinoma model Oncogene High 29321668
2019 CLIP-sequencing showed that AATF predominantly binds 45S pre-ribosomal RNA precursor molecules, with binding sites localizing near the SSU cleavage sites. AATF also binds mRNAs encoding ribosome biogenesis factors and snoRNAs. Mass spectrometry interactome analysis confirmed interactions with a large set of proteins involved in rRNA maturation required for small ribosomal subunit (SSU) generation. CLIP-seq, mass spectrometry interactome, RNA-binding analysis Scientific reports High 31363146
2020 Che-1/AATF interacts with RNA polymerase I and the nucleolar upstream binding factor (UBF), promotes RNA polymerase I-dependent transcription, and binds the rDNA promoter, modulating its epigenetic state by competing with HDAC1. Upon DNA damage, Che-1 relocalizes from rDNA to the TP53 promoter. Co-immunoprecipitation, ChIP, rRNA synthesis assay, RNAi, nucleolar morphology analysis Nucleic acids research High 32421830
2020 Che-1/AATF promotes cell proliferation in multiple myeloma by directly interacting with histones and displacing HDAC class I members from them, sustaining global histone acetylation and gene expression. Transgenic mice expressing human Che-1 in plasma cells develop multiple myeloma. Co-immunoprecipitation, histone acetylation assay, transgenic mouse model, siRNA Blood advances High 33186461
2021 CK2 protein kinase phosphorylates Che-1/AATF at Ser316, Ser320, and Ser321 in vitro and in vivo. These phosphorylation events are required for Che-1/histone H3 binding and for Che-1's pro-proliferative activity. In vitro kinase assay, 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 produces marked accumulation of RNA:DNA hybrids (R-loops), which triggers sustained activation of an interferon gene expression signature, indicating that Che-1/NEAT1 cooperation prevents excessive inflammatory signaling by facilitating R-loop clearance. Co-immunoprecipitation with NEAT1, R-loop immunoprecipitation (S9.6 antibody), RNA-seq, siRNA, paraspeckle localization imaging The EMBO journal High 35929179
2022 AATF competitively interacts with nuclear AIF (apoptosis-inducing factor) to inhibit AIF from binding DNA, thereby inhibiting parthanatos in neuronal ischemia-reperfusion models. AATF overexpression reduced infarct volume and neuronal death in a dMCAO/R model. Co-immunoprecipitation, competitive binding assay, DNA fragmentation assay, OGD/R and dMCAO/R models, viral overexpression Journal of molecular neuroscience Medium 36058992
2025 AATF interacts with XRCC4 (a core NHEJ subunit), preventing its ubiquitin-mediated proteasomal degradation. Upon DNA damage, ATM phosphorylates AATF at Ser189, causing its dissociation from XRCC4 and enabling rapid XRCC4 recruitment to DNA break sites for efficient NHEJ repair. AATF depletion or expression of phosphorylation-deficient AATF impaired NHEJ and sensitized glioblastoma xenografts to chemoradiotherapy. Co-immunoprecipitation, mass spectrometry, in vitro phosphorylation assay, site-directed mutagenesis, NHEJ assay, xenograft model Nature communications High 40436899

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 261 10200473
2016 Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex. Molecular cell 150 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) 138 12588839
2006 Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer cell 109 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 70 26494467
2014 Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly. Nature communications 68 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
2007 NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. Journal of cell science 53 17488777
2020 Controlling Cell Death through Post-translational Modifications of DED Proteins. Trends in cell biology 52 32302548
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
2015 Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53. Cell death & disease 34 25996291
2012 The Azospirillum brasilense Che1 chemotaxis pathway controls swimming velocity, which affects transient cell-to-cell clumping. Journal of bacteriology 33 22522896
2023 [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data. Journal of neuroinflammation 30 36906584
2006 Functional characterization of AATF transcriptome in human leukemic cells. Molecular and cellular biochemistry 30 17006618
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 29 34384756
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
2019 Long and short isoforms of c-FLIP act as control checkpoints of DED filament assembly. Oncogene 28 31740779
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 24 28214471
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
2024 Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis. Nature communications 22 38710704
2022 DED Interaction of FADD and Caspase-8 in the Induction of Apoptotic Cell Death. Journal of microbiology and biotechnology 20 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
2019 A protein-RNA interaction atlas of the ribosome biogenesis factor AATF. Scientific reports 17 31363146
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
2011 The chemotaxis-like Che1 pathway has an indirect role in adhesive cell properties of Azospirillum brasilense. FEMS microbiology letters 16 22092709
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
2014 HIPK2 sustains apoptotic response by phosphorylating Che-1/AATF and promoting its degradation. Cell death & disease 13 25210797
2020 AATF and SMARCA2 are associated with thyroid volume in Hashimoto's thyroiditis patients. Scientific reports 12 32019955
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
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
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 10 35329844
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
2014 Oncogenic nature of a novel mutant AATF and its interactome existing within human cancer cells. Cell biology international 10 25231211
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 BFR2: a curated ribosomal reference dataset for benthic foraminifera. Scientific data 9 39604449
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
2024 Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes. Nature communications 8 39419969
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
2025 Elevated nonhomologous end-joining by AATF enables efficient DNA damage repair and therapeutic resistance in glioblastoma. Nature communications 7 40436899
2023 Modified Danzhi Xiaoyao Powder (MDXP) improves the corneal damage in dry eye disease (DED) mice through phagocytosis. Journal of ethnopharmacology 7 38070838
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
1987 The sequence of chromosome 3 loci AHSG:TF:CHE1. Human heredity 7 3557458
2024 TACE inhibition: a promising therapeutic intervention against AATF-mediated steatohepatitis to hepatocarcinogenesis. Molecular oncology 5 38558505
2024 Targeting type I DED interactions at the DED filament serves as a sensitive switch for cell fate decisions. Cell chemical biology 5 39053461
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
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
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
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