Affinage

DAXX

Death domain-associated protein 6 · UniProt Q9UER7

Length
740 aa
Mass
81.4 kDa
Annotated
2026-06-09
100 papers in source corpus 59 papers cited in narrative 59 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DAXX is a multifunctional nuclear scaffold and ATP-independent molecular chaperone that links chromatin assembly, transcriptional repression, and stress/apoptotic signaling, operating predominantly from PML nuclear bodies under steady state (PMID:10684855, PMID:34408321). As a dedicated histone H3.3 chaperone it partners with ATRX to deposit H3.3 and maintain a repressed, H3K9me3-marked chromatin state at telomeres, pericentromeres, and tandem repetitive/retrotransposon elements, recruiting SUV39H to catalyze H3K9 trimethylation and methyltransferases that mark new H3.3-H4 prior to DNA deposition (PMID:26340527, PMID:36868228). Structural and biochemical dissection resolves DAXX into mechanistically distinct complexes: an ATRX-DAXX complex governing telomeric chromatin and an ATRX-independent DAXX-SETDB1-KAP1-HDAC1 complex silencing endogenous retroviruses, with H3.3 binding itself stabilizing DAXX protein (PMID:29084956). DAXX additionally guards genome stability at centromeres in an ATRX-independent, H3.3-deposition-independent manner by preventing R-loop accumulation and double-strand breaks, and its loss compromises p53 chromatin binding genome-wide (PMID:38038252, PMID:36028493). As a transcriptional co-repressor it binds sumoylated factors through phosphorylation-regulated SUMO-interacting motifs and recruits HDAC1 and DNMT1 to silence targets, a logic exemplified by SUMO-dependent repression of Smad4 and RelB-directed DNMT1 recruitment to NF-κB target promoters (PMID:15637079, PMID:18413714, PMID:21474068). DAXX stabilizes MDM2 by bridging it to the deubiquitinase USP7/Hausp and is released upon ATM-dependent Ser564 phosphorylation during DNA damage to permit MDM2 self-degradation and p53 activation (PMID:16845383, PMID:23405218). In its chaperone capacity DAXX uses a polyD/E region to prevent and reverse aggregation of clients including p53 and MDM2 (PMID:34408321). DAXX governs apoptosis bidirectionally—binding the Fas death domain and activating the ASK1-JNK pathway in the cytoplasm while acting anti-apoptotically in the nucleus, with the balance set by its regulated localization (PMID:9215629, PMID:9743501, PMID:11495919). DAXX broadly restricts viruses, silencing retroviral and herpesviral DNA via HDAC/DNMT recruitment and blocking incoming HIV-1 cores and an early SARS-CoV-2 step through SIM- and D/E-domain-dependent mechanisms (PMID:15795247, PMID:23221555, PMID:32545337, PMID:35508460). Its localization and activity are controlled by phosphorylation (ATM, CK2, HIPK1), sumoylation, and partners including PML, DJ-1, and importin alpha3 (PMID:10684855, PMID:12529400, PMID:15983381, PMID:17661348, PMID:21474068).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Establishing how Fas engagement is transduced, DAXX was shown to bind the Fas death domain and to activate the JNK pathway through ASK1, defining a FADD-independent apoptotic branch.

    Evidence Yeast two-hybrid, co-IP with dominant-negative and kinase-dead ASK1 mutants, apoptosis assays

    PMID:9215629 PMID:9743501

    Open questions at the time
    • Did not resolve the nuclear functions of DAXX
    • Physiological relevance of overexpression-based pro-apoptotic activity unaddressed
  2. 1999 High

    Genetic knockout in mice unexpectedly showed DAXX is required to suppress apoptosis in the embryo, reframing it as anti-apoptotic in vivo and exposing a paradox with its overexpression phenotype.

    Evidence Targeted gene deletion in mice with embryonic phenotyping

    PMID:10444590

    Open questions at the time
    • Molecular basis of the anti-apoptotic requirement not defined
    • Did not distinguish nuclear vs cytoplasmic contributions
  3. 2003 High

    Endogenous depletion studies reconciled the paradox by showing DAXX is anti-apoptotic and a transcriptional repressor of NF-κB/E2F1 targets, while also being required for stress-induced JNK death in primary cells.

    Evidence RNAi/siRNA knockdown with Bcl-2 rescue, transcriptional target analysis, UV/oxidative stress and PML co-silencing epistasis

    PMID:12482920 PMID:14517282 PMID:15861194

    Open questions at the time
    • Direct transcriptional target promoters not all mapped
    • Switch between pro- and anti-apoptotic states not mechanistically defined
  4. 2003 High

    DAXX localization emerged as the control point for its dual function: PML, HIPK1, ASK1, and DJ-1 partition DAXX between PML bodies, chromatin, and cytoplasm, gating repressor versus apoptotic activity.

    Evidence Co-IP, immunofluorescence, kinase/phospho-site mutagenesis (HIPK1 Ser669), PML-KO and DJ-1 mutant epistasis

    PMID:10684855 PMID:11495919 PMID:12529400 PMID:15983381

    Open questions at the time
    • Quantitative thresholds governing redistribution unclear
    • Integration of multiple localization inputs not unified
  5. 2005 High

    DAXX was defined as a SUMO-dependent co-repressor that reads sumoylated transcription factors and recruits HDAC/DNMT machinery, providing the molecular logic for gene silencing.

    Evidence ChIP, SUMO-site mutagenesis (Smad4 K159), in vitro binding, RNAi rescue; DMAP1/DNMT1 complex co-IP

    PMID:14978102 PMID:15637079

    Open questions at the time
    • Generality across SUMO substrates not established at this stage
    • Direct DAXX SIM determinants not yet mapped
  6. 2006 High

    DAXX was shown to control the p53/MDM2 axis by bridging MDM2 to the deubiquitinase USP7/Hausp to stabilize MDM2, then releasing MDM2 upon DNA damage to activate p53.

    Evidence Co-IP, siRNA knockdown, MDM2 stability and ubiquitination assays, DNA damage dissociation

    PMID:16845383

    Open questions at the time
    • Damage signal driving dissociation not yet identified
    • Whether DAXX directly modifies MDM2 unresolved
  7. 2008 High

    DAXX was placed at the apex of epigenetic gene silencing by recruiting DNMT1 to RelB target promoters and methylating their DNA, linking transcriptional repression to heritable promoter methylation.

    Evidence ChIP for Dnmt1, daxx-/- and relB-/- cell lines, DNA methylation assays, rescue by Daxx restoration

    PMID:16982744 PMID:18413714

    Open questions at the time
    • Mechanism of DNMT1 recruitment specificity unclear
    • Scope of methylation targets beyond RelB genes undefined
  8. 2011 High

    Structural and kinase studies dissected the DAXX SUMO-interacting motifs, showing CK2 phosphorylation tunes SUMO-1 paralog selectivity and an intramolecular SIM-N autoregulatory mechanism, providing the biophysical basis for SUMO-dependent recruitment.

    Evidence NMR structures of SIM:SUMO complexes, CK2 kinase and phospho-site mutagenesis, binding affinity measurements, apoptosis reporters

    PMID:21383010 PMID:21474068

    Open questions at the time
    • In vivo impact of paralog selectivity on specific targets not fully mapped
    • Coordination of two SIMs in native complexes unclear
  9. 2012 Medium

    DAXX was established as an H3.3 chaperone acting with ATRX to deposit H3.3 and maintain repressed chromatin at centromeric/pericentromeric and transgene loci, redirecting its function toward heterochromatin maintenance.

    Evidence Live-cell imaging, FRAP, ChIP for H3.3 and histone marks under heat shock, ATRX-negative cell comparison, ICP0-induced activation

    PMID:22572957 PMID:22976303

    Open questions at the time
    • Whether repression and H3.3 deposition are separable not yet resolved
    • Single-locus models may not generalize genome-wide
  10. 2013 High

    The damage signal releasing DAXX from MDM2 was identified as ATM-dependent Ser564 phosphorylation, closing the loop on how DNA damage converts DAXX from an MDM2 stabilizer to a p53 activator.

    Evidence Phospho-specific antibodies, ATM inhibitor/KO, Ser564 mutagenesis, Daxx-Mdm2 co-IP after damage

    PMID:23405218

    Open questions at the time
    • Reconciliation with later reports of no p53 transcriptional effect needed
    • Phosphatase counter-regulation not addressed here
  11. 2015 High

    Genome-wide profiling demonstrated DAXX/ATRX targets repetitive elements and telomeres, with SUV39H-dependent H3K9me3 enforcing repression, defining the mechanism of heterochromatin-based repeat silencing.

    Evidence ChIP-seq, RNA-seq, siRNA knockdown, DNA hypomethylation treatment, H3K9me3 ChIP

    PMID:26340527

    Open questions at the time
    • Order of H3.3 deposition versus H3K9me3 not yet established
    • Upstream recruitment factors for repeat targeting unclear
  12. 2017 High

    Crystallography of the ATRX-DAXX interface and complex purification resolved DAXX into two distinct repressive assemblies—ATRX-DAXX for telomeres and DAXX-SETDB1-KAP1-HDAC1 for ERVs—and showed H3.3 binding stabilizes DAXX even without nucleosomal incorporation.

    Evidence X-ray crystallography, single-residue mutagenesis, biochemical complex purification, RNA-seq, ChIP; PTEN-DAXX co-IP and H3.3 ChIP

    PMID:28497778 PMID:29084956

    Open questions at the time
    • How DAXX is partitioned between the two complexes in cells unclear
    • Non-nucleosomal H3.3 functions incompletely defined
  13. 2021 High

    DAXX was shown to be an ATP-independent chaperone/disaggregase via its polyD/E region, unifying its scaffolding roles with direct protein quality control of clients p53 and MDM2.

    Evidence In vitro aggregation/disaggregation assays, polyD/E deletion mutants, p53/MDM2 client and tumor-mutant functional assays; Morc3 SUMO-dependent upstream recruitment

    PMID:34408321 PMID:34650047

    Open questions at the time
    • Full client repertoire in vivo unknown
    • Relationship between chaperone and chromatin functions not integrated
  14. 2022 High

    DAXX/ATRX loss was shown to impair p53 chromatin binding and DNA damage response genome-wide via H3.3 depletion, connecting DAXX's chromatin chaperone role to tumor-suppressor function.

    Evidence DAXX/ATRX knockout, ChIP-seq (p53, H3.3, γH2AX), ATAC-seq, RNA-seq

    PMID:36028493

    Open questions at the time
    • Causal sequence between H3.3 loss and p53 binding defect not fully resolved
    • ALT acquisition as confounder
  15. 2022 High

    DAXX was established as a broad antiviral restriction factor that silences viral DNA (retroviruses, herpesviruses) and blocks early steps of HIV-1 and SARS-CoV-2 through SIM- and D/E-domain-dependent mechanisms, with viruses encoding countermeasures to degrade it.

    Evidence ChIP on viral DNA, co-IP with DNMTs/capsid factors, SIM and D/E domain mutants, CRISPR screen, proteasome and PLpro/pp71/BNRF1 degradation studies

    PMID:19369322 PMID:22102817 PMID:23221555 PMID:32545337 PMID:35508460

    Open questions at the time
    • Whether one DAXX activity underlies all antiviral effects unclear
    • Capsid-binding mechanism not structurally defined
  16. 2024 High

    DAXX was found to protect centromere genome stability by preventing R-loop accumulation and DSBs in an ATRX- and H3.3-deposition-independent but H3.3-binding-dependent manner, separating a chromatin-protective role from transcriptional silencing.

    Evidence DAXX depletion in glioma/pNET lines, DRIP-seq and S9.6 immunofluorescence, γH2AX assays, H3.3 interaction mutants, BRCA1 localization

    PMID:38038252

    Open questions at the time
    • How H3.3-bound DAXX suppresses R-loops mechanistically unclear
    • Relationship to BRCA1 recruitment not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DAXX's multiple modular activities—H3.3 chaperone/disaggregase, SUMO-dependent co-repressor, MDM2/p53 regulator, and antiviral restriction—are coordinately partitioned and prioritized within a single cell under given signals remains unresolved.
  • No unified model linking localization control to selection among competing activities
  • Quantitative stoichiometry of distinct DAXX complexes in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005730 nucleolus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-392499 Metabolism of proteins 2
Partners
ASK1ATRXDJ-1DNMT1HDAC1MDM2PMLUSP7
Complex memberships
ATRX-DAXX complexDAXX-DMAP1-DNMT1 complexDAXX-SETDB1-KAP1-HDAC1 complexPML nuclear bodies

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 DAXX (Daxx) was identified as a novel protein that binds specifically to the Fas death domain via its C-terminal portion. A different region of Daxx activates both JNK and apoptosis. Overexpression of Daxx enhances Fas-mediated apoptosis and activates the JNK pathway. The Fas-binding domain of Daxx acts as a dominant-negative inhibitor of both Fas-induced apoptosis and JNK activation, and Daxx and FADD define two distinct apoptotic pathways downstream of Fas. Yeast two-hybrid, co-immunoprecipitation, overexpression with dominant-negative mutants, apoptosis assays Cell High 9215629
1998 Daxx activates the JNK kinase kinase ASK1 downstream of the Fas receptor. Upon Fas activation, Daxx interacts with ASK1 and relieves an inhibitory intramolecular interaction between the N- and C-termini of ASK1, thereby activating its kinase activity. Overexpression of a kinase-deficient ASK1 mutant inhibited Fas- and Daxx-induced apoptosis and JNK activation. Co-immunoprecipitation, kinase-deficient mutant rescue experiments, apoptosis assays Science (New York, N.Y.) High 9743501
1999 Genetic knockout of Daxx in mice results in extensive apoptosis and embryonic lethality rather than the hyperproliferative phenotype expected from loss of a pro-apoptotic gene, establishing that Daxx is required to suppress apoptosis in the early embryo. Targeted gene deletion in mice, embryonic phenotypic analysis Genes & development High 10444590
2000 PML and Daxx physically interact within PML nuclear bodies (NBs). In the absence of PML, Daxx acquires a dispersed nuclear pattern and activation-induced cell death of splenocytes is profoundly impaired. PML inactivation completely abrogates Daxx's pro-apoptotic ability, placing PML upstream of Daxx in a nuclear body-dependent apoptotic pathway. Co-immunoprecipitation, immunofluorescence, PML-knockout cell/mouse models, apoptosis assays The Journal of experimental medicine High 10684855
2000 Daxx interacts with the ETS1 transcription factor (via its C-terminal 173 amino acid region binding to the ETS1 N-terminal 139 amino acids) and represses ETS1-mediated transcriptional activation of target genes MMP1 and BCL2. Co-localization of EAP1/Daxx and ETS1 in the nucleus was confirmed in mammalian cells. Yeast two-hybrid, in vitro binding, co-localization, transcriptional reporter assays with deletion mutants Oncogene Medium 10698492
2000 Daxx interacts with Sentrin/SUMO and its conjugating enzyme Ubc9. The Fas-binding C-terminal region of Daxx (amino acids 625-740) maps as the sentrin and Ubc9 binding region, suggesting regulatory overlap between SUMO modification and Fas signaling at this domain. Yeast two-hybrid, GST pull-down, co-immunoprecipitation Biochemical and biophysical research communications Medium 11112409
2000 Phosphorylated dimers of HSP27 interact with Daxx, preventing Daxx's interaction with both ASK1 and Fas, and blocking Daxx-mediated apoptosis. HSP27 also blocks Fas-induced translocation of Daxx from the nucleus to the cytoplasm. A Daxx mutant lacking the HSP27 binding domain is not inhibited, and an HSP27 phosphorylation mutant (oligomer-only form) does not inhibit Daxx. Co-immunoprecipitation, immunofluorescence, apoptosis assays with phosphorylation and binding domain mutants Molecular and cellular biology High 11003656
2001 ASK1 controls the subcellular localization of Daxx: ASK1 sequesters Daxx in the cytoplasm, preventing its nuclear transcriptional repressor activity and enabling Daxx to bind activated Fas and mediate apoptosis. The relative concentration of ASK1 determines whether Daxx functions as a cytoplasmic pro-apoptotic mediator or a nuclear transcriptional repressor. Immunofluorescence, transcriptional reporter assay, co-expression studies The Journal of biological chemistry Medium 11495919
2003 RNAi-mediated depletion of endogenous DAXX increases apoptosis (rescued by Bcl-2 overexpression) and causes transcriptional de-repression, including upregulation of NF-κB- and E2F1-regulated target genes, establishing that endogenous DAXX has anti-apoptotic and transcriptional repressor functions. RNAi knockdown, apoptosis assays, Bcl-2 rescue, transcriptional reporter/target gene analysis Journal of cell science High 12482920
2003 siRNA-mediated Daxx silencing sensitizes cells to Fas- and stress-induced apoptosis, with caspase activation, cytochrome c release, and JNK activation. Daxx silencing has no apparent cytotoxic effects alone; PML silencing has no effect on Daxx silencing-mediated apoptosis, suggesting Daxx inhibits Fas/stress apoptosis by suppressing proapoptotic gene expression outside PML domains. siRNA knockdown, apoptosis assays (caspase activation, cytochrome c release, JNK activation), PML co-silencing epistasis Molecular and cellular biology High 14517282
2003 HIPK1 physically interacts with Daxx and relocalizes it from PML oncogenic domains (PODs) to chromatin, disrupting Daxx-PML interaction and augmenting Daxx interaction with HDAC1. HIPK1 also phosphorylates Daxx at Ser669; phosphorylation of this site diminishes Daxx transcriptional repression activity at specific promoters. Relocation from PODs is phosphorylation-independent but requires an active HIPK1 kinase domain. Co-immunoprecipitation, immunofluorescence, kinase assay, phospho-site mutagenesis, transcriptional reporter assays Molecular and cellular biology High 12529400
2004 Daxx interacts with DMAP1 (DNA methyltransferase 1-associated protein), and both form a complex with DNMT1 and co-localize in the nucleus. DMAP1 enhances Daxx-mediated repression of glucocorticoid receptor transcriptional activity, and Daxx protects DMAP1 from protein degradation in vivo. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, transcriptional reporter assays Journal of immunology Medium 14978102
2005 Wild-type DJ-1 sequesters Daxx in the nucleus, preventing Daxx from translocating to the cytoplasm, binding ASK1, and triggering the ASK1-dependent apoptotic pathway. The disease-causing L166P mutant of DJ-1 fails to sequester Daxx. DJ-1 was identified as a Daxx-interacting protein. Yeast two-hybrid screen, co-immunoprecipitation, immunofluorescence, apoptosis assays with DJ-1 mutants Proceedings of the National Academy of Sciences of the United States of America High 15983381
2005 Daxx mediates SUMO-dependent transcriptional repression of Smad4 via the C-terminal domain of Daxx. Daxx-Smad4 interaction requires sumoylation of Smad4 at Lys159 (but not Lys113). ChIP confirmed Daxx recruitment to an endogenous Smad4-targeted promoter in a Lys159-sumoylation-dependent manner. Daxx knockdown by RNAi enhanced TGF-β-induced transcription through a Smad4-dependent, but not K159R-Smad4-dependent, manner. Co-immunoprecipitation, in vitro binding, SUMO site mutagenesis, chromatin immunoprecipitation (ChIP), RNAi knockdown, transcriptional reporter assays The Journal of biological chemistry High 15637079
2005 Daxx interacts with avian sarcoma virus (ASV) integrase and viral DNA (via IN), and recruits histone deacetylases (HDACs) to viral DNA, repressing viral gene expression as an antiviral response. HDAC association with viral DNA is Daxx-dependent. Daxx is not required for early integration steps but restricts viral reporter gene expression. Yeast two-hybrid, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), viral transduction assays in Daxx-null vs. Daxx-expressing cells Journal of virology High 15795247
2005 Daxx is required for stress-induced cell death and JNK activation in primary fibroblasts. RNAi depletion of Daxx in primary fibroblasts renders cells resistant to UV irradiation- and oxidative stress-induced cell death and impairs MKK/JNK activation, establishing a pro-apoptotic role in physiological settings. RNAi knockdown in primary fibroblasts, UV/H2O2 stress assays, JNK activation assays Cell death and differentiation Medium 15861194
2006 Daxx is required for Mdm2 stability. Daxx simultaneously binds Mdm2 and the deubiquitinase Hausp/USP7, mediating the stabilizing effect of Hausp on Mdm2. Daxx also enhances the intrinsic E3 ubiquitin ligase activity of Mdm2 toward p53. Upon DNA damage, Daxx dissociates from Mdm2, correlating with Mdm2 self-degradation and p53 activation. Co-immunoprecipitation, siRNA knockdown, Mdm2 stability assays, ubiquitination assays, DNA damage experiments Nature cell biology High 16845383
2006 Daxx represses antiapoptotic genes regulated by NF-κB by interacting with RelB. Daxx forms complexes with RelB while bound to target sites in the cIAP2 promoter (shown by EMSA and ChIP). daxx-/- cells show elevated murine c-IAP mRNA/protein levels, while relB-/- cells show reduced levels. Daxx-mediated sensitization to apoptosis is mechanistically linked to its transcriptional repression through RelB. Co-immunoprecipitation, EMSA, ChIP, daxx-/- and relB-/- mouse embryo cell lines, mRNA/protein level analysis Cancer research High 16982744
2006 Daxx interacts with Tcf4 and reduces Tcf4 DNA binding activity and transcriptional activity in the nucleus. Daxx overexpression alters expression of Tcf4 downstream genes (cyclin D1, Hath-1) and induces G1 phase arrest in colon cancer cells. Yeast two-hybrid, co-immunoprecipitation, transcriptional reporter assays, cell cycle analysis The Journal of biological chemistry Medium 16569639
2007 Axin directly associates with Daxx at endogenous levels and tethers Daxx to p53. The Daxx/Axin complex formation is enhanced by UV irradiation. Axin cooperates with Daxx to stimulate HIPK2-mediated Ser46 phosphorylation of p53 and selectively activates p53 target PUMA. Daxx fails to inhibit colony formation in Axin-/- cells, and UV-induced cell death is attenuated by knockdown of Axin and Daxx. Co-immunoprecipitation (endogenous), UV irradiation assays, Axin-/- cell epistasis, siRNA knockdown, p53 phosphorylation assay, colony formation assay Cancer research High 17210684
2007 Daxx represses NF-κB transcriptional activity by interacting with p65 and inhibiting p300/CBP-mediated acetylation of p65. Co-immunoprecipitation revealed endogenous Daxx-p65 interaction stimulated by TNFα. ChIP and EMSA confirmed Daxx-mediated repression of NF-κB on target gene promoters. Co-immunoprecipitation, ChIP, EMSA, acetylation assays Journal of molecular biology Medium 17362989
2007 Daxx is a transcriptional co-repressor of C/EBPβ. Daxx directly interacts with C/EBPβ via amino acids 190-400 of Daxx; co-expression of C/EBPβ relocates Daxx from PODs to the nucleoplasm. Daxx suppresses C/EBPβ basal and p300-enhanced transcriptional activity by decreasing p300-mediated C/EBPβ acetylation. PML co-expression abrogates the repressive Daxx-C/EBPβ interaction by re-recruiting Daxx to PODs. GST pull-down, co-immunoprecipitation, immunofluorescence, transcriptional reporter assays, acetylation assays The Journal of biological chemistry Medium 19690170
2007 STRESS-DEPENDENT CHIP-Daxx interaction: CHIP (a ubiquitin E3 ligase/co-chaperone) interacts with Daxx in a stress-dependent manner, ubiquitinating Daxx at Lys630/631 (competing with sumoylation machinery), partitioning Daxx to an insoluble compartment, blocking HIPK2 association with Daxx, preventing p53 Ser46 phosphorylation, and suppressing the p53-dependent apoptotic program. Co-immunoprecipitation, in vitro ubiquitination assay, mutagenesis (Lys630/631), microarray, p53 phosphorylation assays, CHIP KO MEFs The Journal of biological chemistry High 19465479
2008 Daxx controls epigenetic silencing of RelB target genes (dapk1, dapk3, c-flip, birc3) by recruiting DNA methyltransferase 1 (Dnmt1) to target gene promoters in a RelB-dependent manner, resulting in promoter DNA methylation. daxx-/- cells show decreased methylation of target promoters, and restoration of Daxx in daxx-/- cells restores DNA methylation. ChIP, daxx-/- and relB-/- cell lines, mRNA/protein level analysis, DNA methylation assays, stable transfection rescue Genes & development High 18413714
2008 Daxx contains two functional nuclear localization signals (NLS1: RLKRK at residues 227-231; NLS2: KKSRKEKK at residues 630-637) and interacts selectively with importin alpha3 through both NLS sequences. NLS2 plays the major role; disrupting both NLS1 and NLS2 is required to completely block nuclear localization and PML body association. Nuclear localization of Daxx is essential for its transcriptional effects on GR and p53. Site-directed mutagenesis, domain analysis, co-immunoprecipitation with importin alpha3, immunofluorescence, transcriptional reporter assays Journal of cellular biochemistry High 17661348
2006 In response to DNA damage, Daxx localized in PML-NBs undergoes ubiquitination and degradation. RASSF1C, a newly identified Daxx binding partner, is constitutively anchored by Daxx in PML-NBs but is released and translocates to cytoplasmic microtubules when Daxx is degraded, where it participates in SAPK/JNK activation, coupling nuclear DNA damage to cytoplasmic SAPK/JNK signaling. Co-immunoprecipitation, immunofluorescence, ubiquitination assays, DNA damage (UV/chemicals), JNK activation assays The EMBO journal High 16810318
2009 Daxx interacts with STAT3 and functions as a transcriptional co-repressor suppressing IL-6/STAT3-mediated transcription. Type I IFN-induced Daxx suppresses STAT3-mediated transcriptional activation; siRNA-mediated reduction of Daxx enhances IL-6/LIF-induced STAT3-dependent transcription. Daxx and STAT3 co-localize in the nucleus. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, transcriptional reporter assays Oncogene Medium 16331268
2009 HCMV pp71 promotes SUMOylation of its cellular substrate Daxx. Daxx is a transcriptional co-repressor that silences viral immediate-early (IE) genes. At the start of lytic infections, pp71 travels to the nucleus, displaces ATRX from Daxx, and mediates Daxx degradation through a ubiquitin-independent, proteasome-dependent process. SUMOylation assays, co-immunoprecipitation, proteasome inhibitor experiments, viral IE gene expression assays Journal of virology Medium 19369322
2011 DAXX's SUMO-interacting motif (SIM) at residues 732-740 is phosphorylated by CK2 kinase at Ser737 and Ser739. Phosphorylation promotes preferential DAXX-SIM binding to SUMO-1 over SUMO-2/3 (paralog-selective). NMR structural studies show the Daxx-SIM binds SUMO-1 in a parallel orientation. SIM phosphorylation causes Daxx preference for SUMO-1 conjugation/interaction and enhances Daxx-mediated antiapoptotic gene repression under stress. NMR spectroscopy (structural), CK2 kinase assay, phospho-site mutagenesis, SUMO binding assays, apoptosis reporter assays Molecular cell High 21474068
2011 The N-terminal SIM (SIM-N) and C-terminal SIM (SIM-C) of DAXX have distinct SUMO-binding properties characterized by NMR: SIM-N binds SUMO-1 predominantly in a parallel orientation with ~4-fold lower KD than SIM-C; SIM-C interconverts between parallel and antiparallel binding modes. Within native context, SIM-N binds intramolecularly to the adjacent N-terminal helical bundle domain, reducing its apparent affinity for SUMO (putative autoregulatory mechanism). SIM-C interaction with sumoylated Ets1 is SUMO-mediated (no direct Daxx-Ets1 contact). NMR spectroscopy, binding affinity measurements, intramolecular binding assays The Journal of biological chemistry High 21383010
2011 Daxx mediates activation-induced cell death (AICD) in microglia by triggering MST1 signaling. IFN-γ upregulates Daxx expression, which mediates MST1 homodimerization, activation, and nuclear translocation, leading to apoptosis. Depletion of Daxx or MST1 by RNAi attenuates IFN-γ-induced microglial cell death; MST1-null mice show significantly reduced IFN-γ-induced microglial death in vivo. RNAi knockdown, immunofluorescence, apoptosis assays, MST1-null mouse model The EMBO journal High 21572393
2012 Under heat shock, Daxx robustly and reversibly accumulates at centromeric/pericentromeric (CEN/periCEN) heterochromatin from its resting localization in PML NBs. Daxx depletion reduces CEN RNA accumulation under normal conditions and periCEN RNA after heat shock. Daxx depletion also decreases incorporation of the transcription-associated histone variant H3.3 into CEN and periCEN, and perturbs epigenetic modifications (elevating H3K4Me2 at periCEN under heat shock). Immunofluorescence (live-cell localization), FRAP, ChIP for H3.3 and histone modifications, RNA analysis after Daxx depletion, heat shock paradigm Nucleus (Austin, Tex.) Medium 22572957
2012 Daxx and ATRX are required to maintain a repressed chromatin environment at a CMV-promoter-regulated transgene array. In ICP0-expressing HeLa cells, ATRX and Daxx are depleted from the array concomitant with transcriptional activation. Histone H3.3 is recruited to but not incorporated into chromatin at the activated array, suggesting Daxx/ATRX are required for both transcriptional repression and H3.3 chromatin assembly at this locus. ATRX-negative U2OS cells show robust activation of the array. Single-cell live imaging with inducible transgene array, immunofluorescence, siRNA depletion, ATRX-negative cell line comparison Journal of cell science Medium 22976303
2013 Upon DNA damage, Daxx is phosphorylated at Ser564 in an ATM-dependent manner. This phosphorylation disrupts the Daxx-Mdm2 interaction, facilitating Mdm2 self-degradation and p53 activation. Blocking Ser564 phosphorylation (non-phosphorylatable mutant) prevents Daxx-Mdm2 dissociation, stabilizes Mdm2, and inhibits DNA damage-induced p53 activation. Phospho-specific antibodies, ATM inhibitor/KO experiments, Ser564 mutagenesis, Daxx-Mdm2 co-IP after DNA damage, p53 activation assays PloS one High 23405218
2013 USP7 interacts with Daxx and cooperates in regulating mitosis and taxane resistance. USP7 depletion impairs mitotic progression, stabilizes cyclin B, reduces CHFR E3 ubiquitin ligase stability, and consequently accumulates Aurora-A kinase (a CHFR substrate), leading to multipolar mitoses. These effects are independent of p53. Co-immunoprecipitation, siRNA depletion, cell cycle analysis, cyclin B/Aurora-A stability assays, colony formation assays Cell death and differentiation Medium 23348568
2013 Daxx and Rassf1 interact and co-localize during mitosis. Daxx depletion or expression of the Daxx-binding domain of Rassf1 elevates cyclin B stability and increases taxol resistance. Daxx and Rassf1 define a mitotic stress checkpoint enabling cells to exit mitosis as micronucleated cells when encountering mitotic stress (including taxol). Co-immunoprecipitation, immunofluorescence during mitosis, siRNA depletion, cyclin B stability assays, mouse xenograft models Oncogene Medium 21643015
2015 Daxx depletion increases DNA methylation levels at the RASSF1A promoter are critically controlled by DAXX: DAXX overexpression leads to enhanced RASSF1A promoter methylation whereas DAXX inhibition reduces it. p53 recruits DAXX and DNMT1 to the RASSF1A promoter for methylation-mediated silencing. DAXX-mediated RASSF1A methylation also regulates MDM2 protein stability. ChIP, DNA methylation assays, siRNA knockdown, DAXX overexpression, MDM2 stability analysis FASEB journal Medium 23038753
2015 The DAXX/ATRX complex is enriched at tandem repetitive elements (retrotransposons and telomeres) in mouse ESCs; global DNA hypomethylation further promotes this recruitment. DAXX/ATRX knockdown in cells with hypomethylated genomes exacerbates aberrant transcriptional de-repression of repeat elements and telomere dysfunction. Mechanistically, DAXX/ATRX-mediated repression involves SUV39H recruitment and H3K9 trimethylation. Genome-wide binding (ChIP-seq), transcriptome analysis (RNA-seq), siRNA knockdown, DNA hypomethylation treatment, H3K9me3 ChIP Cell stem cell High 26340527
2015 ATM kinase and Wip1 phosphatase are opposing regulators of DAXX phosphorylation at Ser564. ATM-dependent DAXX phosphorylation at S564 (identified by mutagenesis) occurs rapidly during DNA damage response and phosphorylated DAXX localizes to PML nuclear bodies. Wip1 (a p53-regulated phosphatase) dephosphorylates DAXX at S564 both in vitro and in cells. However, DAXX knock-down or TALEN-mediated DAXX deletion did not affect p53-mediated gene expression upon DNA damage. ATM inhibitor, site-directed mutagenesis (S564), in vitro phosphatase assay, immunofluorescence, TALEN-mediated DAXX deletion, RNA-seq/microarray for p53 targets Cell cycle (Georgetown, Tex.) Medium 25659035
2016 Daxx directly binds to the DNA-binding domain of the transcription factor Slug, impeding HDAC1 recruitment and antagonizing Slug E-box binding. This suppresses Slug-mediated EMT and cell invasiveness. Under hypoxia, HIF-1α downregulates Daxx expression, promoting cancer invasion via the HIF-1α/HDAC1/Slug axis. Co-immunoprecipitation, ChIP, siRNA knockdown, EMT/invasion assays, orthotopic mouse model, re-expression rescue experiments Nature communications High 28004751
2017 X-ray crystal structure of the ATRX-DAXX interaction surface was determined at high resolution. Single amino acid substitutions in DAXX that abrogate ATRX complex formation revealed two biochemically distinct DAXX complexes: (1) the ATRX-DAXX complex (gene repression, telomere chromatin structure) and (2) a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation. Histone H3.3 stabilizes DAXX protein levels and can affect DAXX-regulated gene expression without nucleosomal incorporation. X-ray crystallography, single amino acid mutagenesis, biochemical complex purification, RNA-seq (ERV transcription), ChIP Nature communications High 29084956
2017 PTEN interacts with DAXX and directly regulates oncogene expression by modulating DAXX-H3.3 association on chromatin, independently of PTEN's enzymatic phosphatase activity. DAXX inhibition specifically suppresses tumor growth in PTEN-deficient glioma models, associated with global H3.3 genomic redistribution. Co-immunoprecipitation (PTEN-DAXX), ChIP for H3.3, DAXX siRNA knockdown in orthotopic glioma mouse models, RNA-seq Nature communications High 28497778
2017 DAXX is targeted for degradation by the CUL3-SPOP E3 ubiquitin ligase complex, where SPOP acts as the substrate adaptor. Knockdown of SPOP or CUL3 leads to DAXX protein upregulation and inversely correlated downregulation of VEGFR2 mRNA. Simultaneous knockdown of SPOP and DAXX reverses VEGFR2 downregulation, establishing DAXX as the mediating substrate. siRNA knockdown, co-immunoprecipitation, VEGFR2 expression analysis Scientific reports Medium 28216678
2019 Cytoplasmic DAXX physically interacts with p62/SQSTM1 and drives p62 liquid phase condensation by inducing p62 oligomerization. This promotes p62 recruitment of Keap1 and subsequent Nrf2-mediated stress response. DAXX promotes p62 puncta formation in the cytoplasm. Yeast two-hybrid screen, co-immunoprecipitation, immunofluorescence for puncta/condensates, phase separation assays, Nrf2 reporter assays Nature communications High 31434890
2019 ACETYLATION OF SUMO1 MODULATES DAXX-SIM BINDING: Crystal structures of acetylated SUMO1 variants bound to the phosphorylated SIM of Daxx demonstrate that acetylation at K39, K46, or K37 of SUMO1 reduces or eliminates binding to the Daxx phosphoSIM. Acetylation at K37 specifically impacts binding to Daxx but not PML, demonstrating protein-specific structural plasticity in SUMO-SIM interactions. X-ray crystallography, biochemical binding assays with acetylated SUMO1 variants Structure (London, England : 1993) High 31879127
2020 ATRX promotes repair of telomeric DSBs by two mechanisms: (1) promoting cohesion of sister telomeres, and (2) a DAXX-dependent pathway. Loss of telomeric cohesion combined with DAXX deficiency recapitulates all telomeric DSB repair phenotypes associated with ATRX loss (ALT-associated PML bodies, T-SCEs, ECTSs). DAXX has an independent role in telomeric DSB repair. ATRX deletion in mouse cells, DAXX knockdown, telomeric DSB induction, T-SCE assays, APB/ECTS quantification, cohesion assays PLoS biology High 31895940
2020 Daxx loss in the pancreas is well tolerated under normal conditions but creates a permissive transcriptional state (associated with endogenous retroviral element dysregulation) that cooperates with inflammation and Men1 loss to impair pancreas recovery from inflammatory stress. ERV dysregulation by Daxx loss also dysregulates nearby endogenous genes, with corresponding findings in human PanNETs with DAXX mutations. Conditional mouse Daxx knockout, RNA-seq (ERV and gene expression), pancreatitis model, Men1 double-KO Science advances High 32821827
2020 Daxx inhibits HIV-1 reverse transcription and uncoating in a SIM (C-terminal SUMO-interacting motif)-dependent manner. Daxx associates with incoming HIV-1 cores through SIM-dependent interaction with cyclophilin A (CypA) and capsid (CA), and resides in a multiprotein complex with TNPO3, TRIM5α, and TRIM34 on viral capsids. Daxx prevents HIV-1 uncoating in a SIM-dependent manner. Quantitative proteomic screen of HIV-1 core-associated proteins, co-immunoprecipitation, SIM deletion mutants, viral uncoating assays, reverse transcription quantification Viruses High 32545337
2021 DAXX possesses protein-folding activities in an ATP-independent manner via its polyD/E region: DAXX prevents aggregation, solubilizes pre-existing aggregates, and unfolds misfolded species of model substrates and neurodegeneration-associated proteins. DAXX prevents and reverses aggregation of its validated in vivo clients p53 and MDM2, and can restore native conformation and function to tumor-associated, aggregation-prone p53 mutants. In vitro aggregation assays, disaggregation assays, polyD/E deletion mutants, p53/MDM2 client protein functional assays, cell-based assays with p53 mutants Nature High 34408321
2021 Morc3 interacts with Daxx in a SUMO-dependent manner (Morc3 SUMOylation + Daxx SUMO-binding). In Morc3 knockout cells, histone H3.3 is strongly reduced at Morc3-binding sites (ERV regions), and Morc3 mutants that fail to interact with Daxx also fail to maintain ERV H3.3 deposition, establishing Morc3 as a critical upstream regulator of Daxx-mediated H3.3 incorporation. Co-immunoprecipitation, ChIP for H3.3, ATAC-seq, Morc3 KO cells, Morc3 ATPase and SUMOylation mutants Nature communications High 34650047
2022 DAXX and ATRX knockout cells that have acquired ALT-like features show defects in p53 chromatin binding and DNA damage response. ChIP-seq and ATAC-seq revealed genome-wide reduction in p53 DNA-binding and loss of chromatin accessibility at p53 response elements, with depletion of histone H3.3 and accumulation of γH2AX at many p53 sites including subtelomeres. DAXX and ATRX knockout, ChIP-seq (p53, H3.3, γH2AX), ATAC-seq, RNA-seq Nature communications High 36028493
2022 SARS-CoV-2 infection triggers DAXX relocalization to cytoplasmic sites and promotes its degradation. Mechanistically, viral papain-like protease (PLpro) and the proteasome mediate DAXX degradation. DAXX restricts an early, post-entry step of the SARS-CoV-2 life cycle through its D/E domain (also necessary for protein-folding activity), independently of the SUMOylation pathway. CRISPR/Cas9 screen, PLpro expression studies, proteasome inhibitor experiments, DAXX domain mutants, viral replication assays Nature communications High 35508460
2023 DAXX recruits histone methyltransferases to promote H3K9me3 catalysis on new histone H3.3-H4 prior to DNA deposition, providing a de novo H3K9me3 deposition mechanism and a molecular basis for heterochromatin assembly. Exploratory interactomics defined previously uncharacterized histone-dependent complexes in the histone chaperone network. Exploratory interactomics (quantitative proteomics), H3K9 methylation assays, ChIP for H3K9me3, reconstitution experiments Molecular cell High 36868228
2023 DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated lipogenic gene transcription. DAXX associates with lipogenic gene promoters through SREBPs (ChIP). DAXX's SUMO-binding activity (via C-terminal SIM2) is critical for SREBP1/2 activation and lipogenesis; a DAXX SIM2 mutant fails to bind SREBP1/2, has weakened chromatin recruitment, and is defective in promoting lipogenesis and tumor growth. A cell-membrane permeable SIM2 peptide disrupts DAXX-SREBP1/2 interactions and inhibits lipogenesis. Co-immunoprecipitation, ChIP, siRNA knockdown, DAXX SIM mutants, lipidomic analysis, tumor xenograft models, cell-penetrating peptide assay Nature communications High 37045819
2024 DAXX promotes genome stability at centromeres independently of ATRX by preventing R-loop accumulation and DNA double-strand break (DSB) formation. This ATRX-independent function requires DAXX's interaction with histone H3.3 but is independent of H3.3 deposition into nucleosomes and does not reflect centromeric transcription repression. DAXX depletion mobilizes BRCA1 at centromeres, consistent with BRCA1's role in counteracting R-loops. DAXX depletion (siRNA/KO) in glioma and pNET cell lines, R-loop detection (S9.6 immunofluorescence/DRIP-seq), γH2AX quantification at centromeres, H3.3 interaction mutants, BRCA1 localization Nucleic acids research High 38038252
2011 EBV major tegument protein BNRF1 interacts with Daxx at PML nuclear bodies and disrupts the Daxx-ATRX chromatin remodeling complex. Knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines, indicating Daxx and ATRX maintain viral chromatin in a repressed state. Co-immunoprecipitation (BNRF1-Daxx), siRNA knockdown, EBV reactivation assays, domain mapping PLoS pathogens High 22102817
2012 Human Daxx protein levels are increased in response to retroviral (ASV) infection. Daxx is physically associated with both viral DNA and DNA methyltransferases (DNMTs) and is required for long-term viral silencing maintenance and full viral DNA methylation, including initiation of epigenetic repression (repressive histone marks detectable within 12h, LTR DNA methylation within 3 days post-infection). ChIP for Daxx on viral DNA, co-immunoprecipitation with DNMTs, bisulfite methylation assays, Daxx-null cell comparison, time-course analysis Journal of virology High 23221555
2017 During myogenic differentiation, PML NB loss triggers DAXX relocalization from PML NBs to chromocentres. MyoD expression is sufficient to cause PML NB loss. PML silencing induces DAXX relocalization. The C-terminal SUMO-interacting motif of DAXX is required for its co-localization with ATRX in heterochromatin domains during myotube formation. Immunofluorescence, siRNA knockdown of PML, MyoD overexpression, DAXX SIM-C deletion mutants, live imaging Cell death & disease Medium 28358373
2002 HCMV tegument protein pp71 specifically interacts with human Daxx (hDaxx) in a yeast two-hybrid screen and in co-transfection experiments. Co-transfection of hDaxx enhances pp71 recruitment to ND10/PML nuclear bodies. pp71-mediated transactivation of the HCMV major immediate-early enhancer-promoter is synergistically enhanced in the presence of hDaxx. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization, transactivation assays Journal of virology Medium 11992005

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science (New York, N.Y.) 1396 21252315
1997 Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell 813 9215629
1998 Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science (New York, N.Y.) 523 9743501
2013 Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology 352 24148618
2000 Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Molecular and cellular biology 351 11003656
2005 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proceedings of the National Academy of Sciences of the United States of America 277 15983381
1999 Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development. Genes & development 210 10444590
2006 Critical role for Daxx in regulating Mdm2. Nature cell biology 196 16845383
2000 Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis. The Journal of experimental medicine 190 10684855
2018 ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup. Nature communications 178 30315258
2000 EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene 157 10698492
2006 Daxx: death or survival protein? Trends in cell biology 153 16406523
2012 Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 142 22575867
2011 Structural and functional roles of Daxx SIM phosphorylation in SUMO paralog-selective binding and apoptosis modulation. Molecular cell 141 21474068
2002 Functional interaction between the pp71 protein of human cytomegalovirus and the PML-interacting protein human Daxx. Journal of virology 135 11992005
2015 The Daxx/Atrx Complex Protects Tandem Repetitive Elements during DNA Hypomethylation by Promoting H3K9 Trimethylation. Cell stem cell 121 26340527
2011 EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS pathogens 116 22102817
2003 RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX. Journal of cell science 114 12482920
2017 PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3. Nature communications 111 28497778
2003 Daxx silencing sensitizes cells to multiple apoptotic pathways. Molecular and cellular biology 101 14517282
2019 DAXX in cancer: phenomena, processes, mechanisms and regulation. Nucleic acids research 100 31350900
2001 Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm. The Journal of biological chemistry 98 11495919
2005 Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4. The Journal of biological chemistry 95 15637079
2017 Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX. Nature communications 93 29084956
2008 Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation. Genes & development 93 18413714
2003 Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity. Molecular and cellular biology 88 12529400
2019 Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response. Nature communications 85 31434890
2007 Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death. Cancer research 85 17210684
2016 Daxx inhibits hypoxia-induced lung cancer cell metastasis by suppressing the HIF-1α/HDAC1/Slug axis. Nature communications 76 28004751
2005 Daxx is required for stress-induced cell death and JNK activation. Cell death and differentiation 76 15861194
2004 Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1. Journal of immunology (Baltimore, Md. : 1950) 76 14978102
2021 DAXX represents a new type of protein-folding enabler. Nature 74 34408321
2004 DAXX, FLASH, and FAF-1 modulate mineralocorticoid and glucocorticoid receptor-mediated transcription in hippocampal cells--toward a basis for the opposite actions elicited by two nuclear receptors? Molecular pharmacology 72 14978255
2018 Mechanisms of Host IFI16, PML, and Daxx Protein Restriction of Herpes Simplex Virus 1 Replication. Journal of virology 59 29491153
2006 Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation. The EMBO journal 56 16810318
2013 Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. The Journal of biological chemistry 55 23539629
2000 The Daxx enigma. Apoptosis : an international journal on programmed cell death 55 11225842
2023 DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network. Molecular cell 54 36868228
2020 ATRX affects the repair of telomeric DSBs by promoting cohesion and a DAXX-dependent activity. PLoS biology 54 31895940
2013 USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase. Cell death and differentiation 54 23348568
2007 Daxx mediates SUMO-dependent transcriptional control and subnuclear compartmentalization. Biochemical Society transactions 54 18031230
2005 The cellular protein daxx interacts with avian sarcoma virus integrase and viral DNA to repress viral transcription. Journal of virology 53 15795247
2008 PML NBs (ND10) and Daxx: from nuclear structure to protein function. Frontiers in bioscience : a journal and virtual library 48 18508722
2007 Inhibition of NF-kappaB acetylation and its transcriptional activity by Daxx. Journal of molecular biology 47 17362989
2022 Tanshinone IIA inhibits cardiomyocyte apoptosis and rescues cardiac function during doxorubicin-induced cardiotoxicity by activating the DAXX/MEK/ERK1/2 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 46 36182795
2012 Single-cell analysis of Daxx and ATRX-dependent transcriptional repression. Journal of cell science 46 22976303
2012 Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. Journal of virology 46 23221555
2006 Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB. Cancer research 46 16982744
2022 Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen. Nature communications 45 35508460
2021 Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation. Nature communications 45 34650047
2011 Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. The EMBO journal 45 21572393
2009 Human cytomegalovirus protein pp71 induces Daxx SUMOylation. Journal of virology 44 19369322
2022 DAXX-ATRX regulation of p53 chromatin binding and DNA damage response. Nature communications 42 36028493
2000 Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9. Biochemical and biophysical research communications 42 11112409
2018 Long non-coding RNA ChRO1 facilitates ATRX/DAXX-dependent H3.3 deposition for transcription-associated heterochromatin reorganization. Nucleic acids research 41 30335163
2012 Methylation of RASSF1A gene promoter is regulated by p53 and DAXX. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 41 23038753
2019 Rapid and reversible suppression of ALT by DAXX in osteosarcoma cells. Scientific reports 40 30872698
2013 Berberine represses DAXX gene transcription and induces cancer cell apoptosis. Laboratory investigation; a journal of technical methods and pathology 40 23295648
2013 Virion factors that target Daxx to overcome intrinsic immunity. Journal of virology 40 23864634
2014 Clinical features of ATRX or DAXX mutated neuroblastoma. Journal of pediatric surgery 37 25487495
2010 DJ-1 loss by glutaredoxin but not glutathione depletion triggers Daxx translocation and cell death. Antioxidants & redox signaling 37 20014998
2019 Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma. International journal of molecular sciences 36 30625996
2015 Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy. The Journal of biological chemistry 35 25903140
2012 Dualistic function of Daxx at centromeric and pericentromeric heterochromatin in normal and stress conditions. Nucleus (Austin, Tex.) 35 22572957
2006 Physiological and functional interactions between Tcf4 and Daxx in colon cancer cells. The Journal of biological chemistry 35 16569639
2019 DAXX Suppresses Tumor-Initiating Cells in Estrogen Receptor-Positive Breast Cancer Following Endocrine Therapy. Cancer research 31 31387918
2011 Characterizing the N- and C-terminal Small ubiquitin-like modifier (SUMO)-interacting motifs of the scaffold protein DAXX. The Journal of biological chemistry 31 21383010
2020 Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer. Cell death & disease 30 32641734
2011 FTH1 binds to Daxx and inhibits Daxx-mediated cell apoptosis. Molecular biology reports 30 21573799
2011 Regulation of mitosis and taxane response by Daxx and Rassf1. Oncogene 30 21643015
2018 Loss of ATRX/DAXX expression and alternative lengthening of telomeres in uterine leiomyomas. Cancer 29 30423196
2024 HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape. Experimental & molecular medicine 28 38297159
2020 Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo. Science advances 28 32821827
2017 Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 28223336
2015 DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase. Cell cycle (Georgetown, Tex.) 28 25659035
2009 Stress-dependent Daxx-CHIP interaction suppresses the p53 apoptotic program. The Journal of biological chemistry 27 19465479
2017 The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells. Scientific reports 26 28216678
2009 Daxx is a transcriptional repressor of CCAAT/enhancer-binding protein beta. The Journal of biological chemistry 26 19690170
2013 Phosphorylation of Daxx by ATM contributes to DNA damage-induced p53 activation. PloS one 25 23405218
2019 Hotspot DAXX, PTCH2 and CYFIP2 mutations in pancreatic neuroendocrine neoplasms. Endocrine-related cancer 24 30021865
2018 DAXX promotes ovarian cancer ascites cell proliferation and migration by activating the ERK signaling pathway. Journal of ovarian research 24 30336783
2006 Physical and functional interactions between Daxx and STAT3. Oncogene 24 16331268
2003 Long form of cellular FLICE-inhibitory protein interacts with Daxx and prevents Fas-induced JNK activation. Biochemical and biophysical research communications 24 14637155
2010 DAXX is a new AIRE-interacting protein. The Journal of biological chemistry 22 20185822
2023 Endoscopic ultrasound fine-needle biopsy to assess DAXX/ATRX expression and alternative lengthening of telomeres status in non-functional pancreatic neuroendocrine tumors. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 21 37169669
2019 Acetylation of SUMO1 Alters Interactions with the SIMs of PML and Daxx in a Protein-Specific Manner. Structure (London, England : 1993) 21 31879127
2007 Physical interactions and functional coupling between Daxx and sodium hydrogen exchanger 1 in ischemic cell death. The Journal of biological chemistry 21 18003619
2004 Physical and functional interactions between Daxx and TSG101. Biochemical and biophysical research communications 21 15033475
2023 DAXX drives de novo lipogenesis and contributes to tumorigenesis. Nature communications 20 37045819
2020 DAXX inhibits cancer stemness and epithelial-mesenchymal transition in gastric cancer. British journal of cancer 20 32203224
2019 DAXX, as a Tumor Suppressor, Impacts DNA Damage Repair and Sensitizes BRCA-Proficient TNBC Cells to PARP Inhibitors. Neoplasia (New York, N.Y.) 20 31029033
2017 Clinicopathological analysis of ATRX, DAXX and NOTCH receptor expression in angiosarcomas. Histopathology 20 28796347
2020 Telomere length alterations and ATRX/DAXX loss in pituitary adenomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19 32203094
2019 Performance of DAXX Immunohistochemistry as a Screen for DAXX Mutations in Pancreatic Neuroendocrine Tumors. Pancreas 19 30747827
2015 Death domain associated protein (Daxx), a multi-functional protein. Cellular & molecular biology letters 19 26540225
2020 Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner. Viruses 18 32545337
2017 Myogenic differentiation triggers PML nuclear body loss and DAXX relocalization to chromocentres. Cell death & disease 18 28358373
2008 Daxx contains two nuclear localization signals and interacts with importin alpha3. Journal of cellular biochemistry 18 17661348
2024 DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks. Nucleic acids research 17 38038252
2023 ATRX/DAXX: Guarding the Genome against the Hazards of ALT. Genes 17 37107548

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