Affinage

DFFB

DNA fragmentation factor subunit beta · UniProt O76075

Length
338 aa
Mass
39.1 kDa
Annotated
2026-06-09
48 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DFFB (DFF40/CAD) is the caspase-activated, Mg2+-dependent endonuclease that executes apoptotic internucleosomal DNA fragmentation, cleaving chromatin in the linker between nucleosomes to generate the characteristic oligonucleosomal DNA ladder (PMID:9560346, PMID:10713148, PMID:11577114). In healthy cells it is held inactive as a heterodimer with DFF45/ICAD, which serves dual roles as a folding chaperone required for the expression of active DFF40 and as a direct steric inhibitor that sequesters the nuclease; caspase-3 and caspase-7 cleave DFF45, releasing fragments and permitting DFF40 to self-assemble into the active enzyme (PMID:9560346, PMID:10318789, PMID:19944011). DFF40 is organized into an N-terminal CIDE-N regulatory domain that mediates DFF45 binding and a C-terminal catalytic domain; its NTD and the DFF45 NTD fold into each other through mutual chaperoning, and the activated enzyme forms a dimeric "molecular scissors" whose deep active-site crevice discriminates internucleosomal from nucleosomal DNA (PMID:9867840, PMID:11371636, PMID:15149602). The CIDE domain forms filament-like assemblies required for nuclease function (PMID:35236824). Catalytically the enzyme is strictly double-strand-DNA specific, requires Mg2+ and physiological K+, is inhibited by Zn2+, and produces blunt or short 5'-overhang ends bearing 5'-phosphate and 3'-hydroxyl groups (PMID:10713148, PMID:11330826, PMID:18283539). Its activity is positively modulated by chromatin and architectural factors — histone H1 binds DFF40 (via its C-terminal domain) to confer DNA-binding ability and increase catalytic efficiency, HMGB1 stimulates cleavage by distorting DNA structure, and polyanions such as heparin and RNA act as inhibitors (PMID:10318789, PMID:15910001, PMID:18239742, PMID:16699957). Efficient fragmentation depends on a cytosolic pool of DFF40 that, upon cytosolic ICAD processing, translocates to chromatin; mislocalization to the nucleoplasm in tumor cells impairs DNA laddering despite intact caspase activation (PMID:22253444, PMID:26755073). In vivo DFFB performs the first intracellular step of cell-free DNA fragmentation, generating the initial nucleosome-patterned cuts (PMID:32004449). Beyond canonical apoptosis, DFF40 loss alters mitochondrial mass, metabolism, and chemotherapy sensitivity (PMID:34678222, PMID:35460011), and sublethal caspase-mediated DFFB activation in cancer persister cells drives DNA damage and ATF3 upregulation that suppresses interferon signaling to enable regrowth (PMID:40894800).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    Established the existence and core logic of DFFB as a caspase-activated nuclease controlled by an inhibitory partner, answering how apoptotic DNA fragmentation is triggered downstream of caspases.

    Evidence Protein purification from Jurkat cells, cDNA cloning, in vitro caspase cleavage and nuclei fragmentation assays

    PMID:9560346

    Open questions at the time
    • Did not resolve the molecular mechanism of inhibition or the structure of the active enzyme
    • Identity of the activating caspases not fully defined
  2. 1999 High

    Defined DFF45 as both chaperone and direct inhibitor, identified caspase-3/-7 (not -6/-8) as the activating proteases, and showed DFF40 oligomerizes to introduce double-strand breaks, with histone H1 as a positive cofactor.

    Evidence In vitro reconstitution, caspase cleavage, co-IP, oligomerization and kinetic assays

    PMID:10318789

    Open questions at the time
    • Structural basis of oligomerization unresolved
    • Mechanism by which H1 stimulates activity not mapped
  3. 1999 High

    Mapped the domain architecture of DFF40 (C-terminal catalytic, N-terminal regulatory/CIDE-N) and the multi-domain binding/inhibition mechanism of DFF45, explaining how caspase cleavage relieves inhibition.

    Evidence Deletion mutagenesis, in vitro nuclease and binding assays (DFF40 domains; DFF45 D1/D2/D3 domains)

    PMID:10527860 PMID:10527861 PMID:9867840

    Open questions at the time
    • Atomic-resolution structure of the heterodimer not yet available
    • How constitutive activity is restrained in vivo unclear
  4. 1999 Medium

    Showed the DFF45 isoform DFF35 inhibits but cannot chaperone DFF40, dissociating the chaperone and inhibitory functions and localizing them to distinct sequence regions.

    Evidence Deletion mutagenesis, nuclease and binding assays

    PMID:10409614

    Open questions at the time
    • Physiological role of DFF35 versus DFF45 in cells not established
    • Single-lab domain mapping
  5. 2000 High

    Provided rigorous biochemical definition of catalytic requirements (Mg2+, pH, dsDNA specificity, internucleosomal preference, end chemistry) and cofactor activation by H1, HMGB1, and topoisomerase II.

    Evidence In vitro endonuclease assays with defined substrates and cofactors, chromatin reconstitution

    PMID:10713148

    Open questions at the time
    • In vivo relevance of individual cofactors not dissected
    • Structural basis of linker-DNA preference not yet shown
  6. 2001 Medium

    Defined the ionic environment for activity, showing K+ in the apoptotic physiological range optimizes activity and ionic strength governs single- versus double-strand cutting.

    Evidence In vitro endonuclease assays under varied ionic conditions

    PMID:11330826

    Open questions at the time
    • Single study, single lab
    • In vivo confirmation of K+ dependence absent
  7. 2001 High

    Genetically established that CAD/DFF40 is required specifically for oligonucleosomal fragmentation and final nuclear disassembly but dispensable for HMW cleavage and early chromatin condensation.

    Evidence CAD-/- DT40 chicken knockout cells, DNA fragmentation and apoptotic morphology analysis

    PMID:11577114

    Open questions at the time
    • Identity of nucleases responsible for HMW cleavage not addressed
    • Avian model; mammalian in vivo requirement shown later
  8. 2001 High

    Solved the solution structure of the DFF40/DFF45 NTD complex, revealing mutual chaperoning via coupled folding and an intermolecular hydrophobic core.

    Evidence NMR solution structure of heterodimeric NTDs with binding analysis

    PMID:11371636

    Open questions at the time
    • Structure of the full catalytic domain not resolved here
    • Does not show the active dimer conformation
  9. 2004 High

    Crystal structure of activated CAD revealed the dimeric 'molecular scissors' architecture and explained how ICAD sequesters monomer and disassembles the dimer, completing the activation mechanism.

    Evidence X-ray crystallography with functional binding and disassembly assays

    PMID:15149602

    Open questions at the time
    • Structure of enzyme bound to DNA/nucleosome not determined
    • Filament-level assembly not captured
  10. 2005 High

    Identified the histone H1 C-terminal domain as the activating element that binds DFF40 and enhances its DNA binding, mechanistically explaining chromatin-dependent stimulation.

    Evidence H1 truncation mutagenesis, binding and nuclease assays across H1 isoforms

    PMID:15910001

    Open questions at the time
    • Structural basis of the H1 CTD–DFF40 interaction unresolved
    • Why isoforms are functionally equivalent despite sequence divergence unexplained
  11. 2006 Medium

    Distinguished cofactor mechanisms: HMGB1 stimulates cleavage by distorting DNA structure rather than binding the enzyme, while polyanions inhibit by blocking DFF40 DNA binding.

    Evidence In vitro nuclease assays with HMGB1 and polyanion truncations/mimics, binding assays

    PMID:16699957 PMID:18239742

    Open questions at the time
    • Physiological concentrations and relevance of polyanion inhibition in cells unclear
    • Single-lab studies
  12. 2008 Medium

    Confirmed strict double-stranded DNA substrate specificity and showed non-substrate nucleic acids act as competitive inhibitors, ruling out RNA degradation as a DFF40 function.

    Evidence In vitro assays with defined oligonucleotides plus in vivo apoptosis time-course

    PMID:18283539

    Open questions at the time
    • Single lab
    • Competitive inhibition relevance in vivo not quantified
  13. 2009 Medium

    Separated DFF45 chaperone activity (requiring its dynamic C-terminal helix) from its inhibitory activity, refining the structural basis of the two ICAD functions.

    Evidence Limited proteolysis, crystallography, chaperone and nuclease assays

    PMID:19944011

    Open questions at the time
    • In vivo consequence of selectively disabling chaperone function not tested
    • Single lab
  14. 2010 Medium

    Demonstrated chromatin-associated localization of the DFF40–DFF45 heterodimer and preferential H1-subtype association upon apoptosis, linking biochemistry to subnuclear positioning.

    Evidence Subcellular fractionation, MNase digestion, co-IP with H1 subtypes in NB4 cells

    PMID:19882353

    Open questions at the time
    • Functional consequence of subtype preference unclear
    • Single cell line
  15. 2016 High

    Established that a cytosolic pool of DFF40 and its proper cytosol-to-chromatin translocation are required for laddering; mislocalization (nucleoplasmic accumulation) impairs fragmentation despite intact caspase signaling.

    Evidence Subcellular fractionation, loss- and gain-of-function rescue in neuroblastoma and glioblastoma cells

    PMID:22253444 PMID:26755073

    Open questions at the time
    • Molecular machinery controlling translocation unidentified
    • Why tumor cells mislocalize DFF40 unknown
  16. 2020 High

    Showed in vivo that DFFB executes the first intracellular cut in cell-free DNA with a distinct, nucleosome-patterned cutting preference, defining its role in cf.DNA biogenesis.

    Evidence DFFB-deficient mouse models with cf.DNA end sequencing and nuclease comparisons

    PMID:32004449

    Open questions at the time
    • Relationship between intracellular DFFB cuts and downstream extracellular processing only partly resolved
    • Tissue sources of cf.DNA not fully dissected
  17. 2022 Medium

    Revealed non-apoptotic and structural roles: CIDE-domain filament assembly is required for nuclease function, and DFF40 loss reprograms mitochondrial mass and metabolism while DFF40 can translocate to mitochondria during cell death.

    Evidence CIDE filament structural study with histone binding (DREP4 ortholog); CRISPR KO Jurkat cells with metabolic profiling and fractionation

    PMID:35236824 PMID:35460011

    Open questions at the time
    • Mechanism linking DFF40 to mitochondrial metabolism unknown
    • Functional role of mitochondrial DFF40 undefined
  18. 2021 Medium

    Linked DFF40 to chemotherapy response and genomic stability, with KO cells showing differential drug sensitivity and impaired H2AX phosphorylation.

    Evidence CRISPR-Cas9 KO Jurkat cells, viability assays, phospho-H2AX analysis

    PMID:34678222

    Open questions at the time
    • Mechanism of impaired DNA damage signaling unclear
    • Single cell type
  19. 2025 Medium

    Implicated sublethal DFFB activation in cancer persistence, where caspase-driven DNA damage and ATF3 upregulation suppress interferon signaling to permit persister regrowth.

    Evidence DFFB-deficient cell lines, ISG and ATF3 perturbation, caspase and DNA damage assays (preprint)

    PMID:40894800

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Direct molecular link from DFFB activity to ATF3 induction not fully resolved
    • Generality across tumor types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DFF40's cytosol-to-chromatin (and mitochondrial) translocation is controlled, and the structural basis of its engagement with nucleosomal substrate, remain open.
  • No structure of DFF40 bound to nucleosomal/linker DNA
  • Trafficking machinery for translocation unidentified
  • Mechanistic basis of non-apoptotic metabolic and persister phenotypes incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 4 GO:0016787 hydrolase activity 3
Localization
GO:0000228 nuclear chromosome 4 GO:0005829 cytosol 2 GO:0005654 nucleoplasm 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-5357801 Programmed Cell Death 4
Partners
CASP3CASP7DFFAHIST1H1 (HISTONE H1)HMGB1TOP2
Complex memberships
DFF40–DFF45 (CAD–ICAD) heterodimer

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DFFB (CPAN/DFF40) is a caspase-activated 40 kDa endonuclease sufficient to degrade naked DNA and induce apoptotic morphology and DNA fragmentation in naive nuclei. Its activity is regulated by DFF45, which is required for CPAN expression and stabilization in an inactive state; proteolytic cleavage of DFF45 by caspases leads to dissociation of DFF45 fragments from CPAN and activation of CPAN endonuclease activity. Protein purification from Jurkat cells, cDNA cloning, in vitro caspase cleavage assay, nuclei fragmentation assay Current biology : CB High 9560346
1999 DFF45 acts as both a molecular chaperone required for proper folding and expression of active DFF40, and as a direct inhibitor of DFF40 nuclease activity. Caspase-3 (but not caspase-6 or caspase-8) and caspase-7 cleave DFF45, causing dissociation of DFF45 fragments from DFF40 and allowing DFF40 to oligomerize into a large functional complex that cleaves DNA by introducing double-strand breaks. Histone H1 directly interacts with DFF40, confers DNA binding ability, stimulates nuclease activity by increasing Kcat and decreasing Km. In vitro reconstitution, caspase cleavage assays, co-immunoprecipitation, oligomerization assays, kinetic enzyme analysis The Journal of biological chemistry High 10318789
1999 DFFB (DFF40) contains a C-terminal catalytic domain (residues 290-345) and an N-terminal regulatory domain (residues 1-83). Deletion of the catalytic domain abolishes caspase-3-induced nuclease activity but not interaction with DFF45. Removal of the regulatory domain yields constitutively active DFF40 that neither binds DFF45 nor requires caspase-3 for activation. The N-terminal regulatory domain is homologous to the CIDE-N domain of DFF45/ICAD and CIDE proteins. Deletion mutagenesis, in vitro nuclease assays, co-immunoprecipitation The Journal of biological chemistry High 9867840
1999 DFF45 interacts with DFF40 through three functional binding domains (D1, D2, D3): D1 binds the activator domain of DFF40, D2 binds the catalytic domain of DFF40. Inhibition of DFF40 nuclease activity arises independently from D1 sequestration of the activator domain and D2 blockage of the catalytic domain. Caspase cleavage of DFF45 disrupts the synergistic binding of its domains to DFF40, resulting in DFF40 activation. Domain deletion analysis, in vitro binding assays, nuclease activity assays Biochemical and biophysical research communications Medium 10527860 10527861
1999 DFF35, an isoform of DFF45, cannot function as a chaperone for DFF40 (unlike DFF45), but binds DFF40 more strongly than DFF45 and inhibits its nuclease activity. The amino acid residues 101-180 of DFF35/45 mediate binding to DFF40, while residues 23-100 (homologous between DFF35/45 and DFF40) function to inhibit DFF40 activity. Deletion mutagenesis, functional nuclease assays, binding assays The Journal of biological chemistry Medium 10409614
2000 DFF40/CAD endonuclease has a pH optimum of 7.5, requires Mg2+ (not Ca2+), is inhibited by Zn2+, generates blunt ends or 1-base 5'-overhangs with 5'-phosphate and 3'-hydroxyl groups, is specific for double-stranded (not single-stranded) DNA, and attacks chromatin preferentially in the internucleosomal linker generating sharp oligonucleosomal DNA ladders. Histone H1, HMGB1, and topoisomerase II activate DFF endonuclease activity on naked DNA substrates. In vitro endonuclease assays with defined substrates, ion/cofactor titration, chromatin reconstitution The Journal of biological chemistry High 10713148
2001 DFF40/CAD nuclease activity requires K+ in the range of 50-125 mM (matching apoptotic cytoplasmic K+ concentrations) for optimal activity (~100-fold higher than at 0 or 200 mM K+); it requires Mg2+, is inhibited by Zn2+ and Cu2+, is active over pH 7.0-8.5, is thermally unstable (inactivated at 42°C), and at high ionic strengths introduces single-stranded nicks rather than double-strand breaks. In vitro endonuclease assays with defined ionic conditions Molecular and cellular biochemistry Medium 11330826
2001 CAD/DFF40 is essential for oligonucleosomal DNA fragmentation during apoptosis in chicken DT40 cells (CAD-/- cells fail to undergo oligonucleosomal fragmentation), but is dispensable for high molecular weight (HMW) DNA cleavage and early-stage (stage I) chromatin condensation. CAD is required for complete nuclear disassembly including final chromatin condensation and nuclear fragmentation. Gene knockout (CAD-/- DT40 cells), DNA fragmentation assays, apoptosis morphology analysis The Journal of biological chemistry High 11577114
2001 The N-terminal domains (NTDs) of both DFF40 and DFF45 are homologous and interact with each other. The NTD of DFF45 alone is unstructured in solution, and its folding is induced upon binding to DFF40 NTD. The solution structure of the heterodimeric NTD complex reveals mutual chaperoning through an extensive intermolecular hydrophobic cluster surrounded by salt bridges. NMR solution structure determination, functional binding analysis Proceedings of the National Academy of Sciences of the United States of America High 11371636
2004 Crystal structure of activated CAD/DFF40 reveals it forms a dimer (molecular scissors) with a deep active-site crevice suited for distinguishing internucleosomal from nucleosomal DNA. ICAD/DFF45 sequesters the nonfunctional CAD/DFF40 monomer and can disassemble the functional CAD/DFF40 dimer through its middle domain; caspase cleavage of ICAD/DFF45 into three domains results in self-assembly of CAD/DFF40 into the active dimer. X-ray crystallography, functional binding and disassembly assays Molecular cell High 15149602
2005 The histone H1 C-terminal domain (CTD) is responsible for activation of DFF40/CAD. The H1 CTD directly binds to DFF40/CAD and confers upon it an increased ability to bind DNA, thereby stimulating linker DNA cleavage. All six somatic cell histone H1 isoforms equally activate DFF40/CAD despite differing CTD primary sequences. Truncation mutagenesis of histone H1, direct binding assays, in vitro nuclease activity assays Biochemistry High 15910001
2006 HMGB1 stimulates DFF40/CAD-mediated DNA cleavage not by binding to DFF40/CAD or enhancing its DNA binding, but by inducing local DNA structural distortions through its HMG-box domains. A structural array of two HMG-boxes is required for stimulation. DNA strand cross-links (cisplatin/transplatin) mimicking HMG-box-induced distortions also affect DFF40/CAD cleavage, suggesting that DNA conformational changes induced by HMG-box binding increase substrate accessibility. In vitro nuclease assays with HMGB1 truncation mutants, DNA binding assays, cisplatin/transplatin cross-linking experiments Acta biochimica Polonica Medium 18239742
2006 Polyanions including RNA, single-stranded DNA, poly-glutamic acid, and heparin inhibit DFF40/CAD endonuclease by binding to the nuclease and impairing its ability to bind double-stranded DNA. Heparin is highly effective at nanomolar concentrations. The inhibitory poly-anions are proposed to bind the positively charged surface formed by alpha4 helices of the DFF40/CAD homodimer. In vitro nuclease competition assays, enzyme-inhibitor binding assays Apoptosis : an international journal on programmed cell death Medium 16699957
2008 DFF40/CAD is exclusively specific for double-stranded DNA; it does not cleave single-stranded DNA, single-stranded RNA, double-stranded RNA, or RNA-DNA heteroduplexes. Non-substrate oligonucleotides of all types competitively inhibit cleavage of double-stranded DNA. In vivo, activation of DFF40/CAD is not temporally correlated with total cellular or nuclear RNA degradation. In vitro nuclease assays with synthetic oligonucleotides of defined composition, in vivo apoptosis time-course analysis Apoptosis : an international journal on programmed cell death Medium 18283539
2009 The C-terminal helix of DFF45 (residues 281-300) is dynamic and necessary for its chaperone activity toward DFF40 but not for inhibition of DFF40 nuclease activity, as determined by limited proteolysis showing residues 1-281 form a rigid domain while the C-terminal loop (residues 277-281) is trypsin-accessible. Limited proteolysis, crystallography, functional nuclease and chaperone assays BMB reports Medium 19944011
2010 DFF40-DFF45 heterodimer localizes to the chromatin-enriched nuclear fraction under both apoptotic and non-apoptotic conditions in NB4 cells. DFF40 interacts with all H1 subtypes tested but preferentially associates with specific H1 subtypes following apoptosis induction by trichostatin A. Subcellular fractionation, MNase digestion, co-immunoprecipitation with histone H1 subtypes, apoptosis induction Apoptosis : an international journal on programmed cell death Medium 19882353
2012 Oligonucleosomal DNA degradation by DFF40/CAD requires a cytosolic pool of the endonuclease. SK-N-AS neuroblastoma cells lacking cytosolic DFF40/CAD fail to undergo DNA laddering despite correct ICAD processing and caspase-3 activation; ICAD is preferentially processed in the cytosolic fraction, allowing DFF40/CAD to translocate from cytosol to chromatin-enriched fraction. Restoring cytosolic DFF40/CAD by overexpression rescues DNA laddering. Subcellular fractionation, overexpression rescue experiment, caspase activity assays, staurosporine-induced apoptosis The Journal of biological chemistry High 22253444
2016 In human glioblastoma cells, DFF40/CAD is improperly accumulated in the nucleoplasmic subcellular compartment rather than the cytosol, impairing oligonucleosomal DNA fragmentation during apoptosis despite correct caspase activation. Overexpression of DFF40/CAD is sufficient to restore DNA laddering after apoptotic challenge in these cells. Subcellular fractionation, overexpression rescue, immunofluorescence, apoptosis assays in GBM cells Neuro-oncology Medium 26755073
2020 DFFB is responsible for the first intracellular step of cell-free DNA fragmentation: analysis of cf.DNA ends in DFFB-deficient mice compared to wild-type mice establishes that DFFB generates the initial intracellular cuts in cf.DNA, with a specific cutting preference distinct from extracellular nucleases DNASE1L3 and DNASE1. The 10 bp periodicity in cf.DNA arises from cutting within intact nucleosomal structure. Nuclease-deficient mouse models, cell-free DNA end analysis, heparin disruption of nucleosomal structure American journal of human genetics High 32004449
2021 DFF40 KO Jurkat T cells generated by CRISPR-Cas9 show chemoresistance to antimetabolites (methotrexate, 6-mercaptopurine, cytarabine) and increased sensitivity to topoisomerase II inhibitors (etoposide, teniposide). DFF40 deficiency impairs histone H2AX phosphorylation following etoposide and cytarabine treatments, suggesting DFF40 regulates genomic stability in the context of chemotherapy response. CRISPR-Cas9 knockout, cell viability assays, phospho-H2AX analysis, flow cytometry Biochemical pharmacology Medium 34678222
2022 DFF40-deficient Jurkat cells exhibit higher mitochondrial mass, increased mtDNA copy number, elevated mitochondrial membrane potential, and higher glycolysis rates (Warburg effect phenotype), with higher Mcl-1 at basal state and resistance to staurosporine- and TBT-induced apoptosis. Cell fractionation shows DFF40 can translocate to the mitochondria following apoptosis induction, suggesting a role in regulating mitochondrial function during cell death. CRISPR-Cas9 KO, cell fractionation, mitochondrial function assays, metabolic profiling Molecular and cellular biochemistry Medium 35460011
2022 The CIDE domain of DFF40 (and its fly orthologue DREP4) forms filament-like assemblies critical for nuclease function. DREP4 CIDE specifically binds histones H1 and H2, an interaction important for nuclease activity. Structural study, CIDE domain filament characterization, histone binding assays, nuclease activity assays Cell death & disease Medium 35236824
2006 DFF40-immunopositive proteins in intact rat liver exist primarily as a 52 kDa form. During hepatic ischemia/reperfusion, caspase-3 activation results in time-dependent accumulation of DFF40-positive fragments (40 and 20 kDa). Immunoprecipitation reveals active caspase-3 is present in the DFF40-immunopositive 20 kDa fraction, suggesting physical association of active caspase-3 with DFF40 cleavage products. Chronic alcohol administration produces similar DFF40 fragmentation. In vivo rat liver injury models, Western blotting, in vitro recombinant caspase-3 digestion, immunoprecipitation Biochemical and biophysical research communications Medium 17011520
2025 In cancer persister cells surviving oncogene-targeted therapy, DFFB (CAD/DFF40) is sublethal activated by apoptotic caspases, induces DNA damage, mutagenesis, and upregulates ATF3. ATF3 then limits AP1-mediated interferon-stimulated gene (ISG) expression, suppressing Type I IFN signaling and enabling persister cell regrowth. DFFB-deficient persister cells exhibit high ISG expression and are unable to regrow. DFFB-deficient cell lines, ISG expression analysis, ATF3 perturbation, caspase activity assays, DNA damage assays bioRxiv : the preprint server for biologypreprint Medium 40894800

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 The Biology of Cell-free DNA Fragmentation and the Roles of DNASE1, DNASE1L3, and DFFB. American journal of human genetics 197 32004449
1998 CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45. Current biology : CB 190 9560346
2005 Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G. Journal of cellular biochemistry 166 15723341
1999 Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1. The Journal of biological chemistry 161 10318789
2000 Cleavage preferences of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease) on naked DNA and chromatin substrates. The Journal of biological chemistry 139 10713148
2004 Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway. Molecular cell 90 15149602
2001 CAD/DFF40 nuclease is dispensable for high molecular weight DNA cleavage and stage I chromatin condensation in apoptosis. The Journal of biological chemistry 87 11577114
2000 The DFF40/CAD endonuclease and its role in apoptosis. Acta biochimica Polonica 82 11996094
2001 Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45. Proceedings of the National Academy of Sciences of the United States of America 77 11371636
1999 Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40. The Journal of biological chemistry 75 10409614
1999 Identification of regulatory and catalytic domains in the apoptosis nuclease DFF40/CAD. The Journal of biological chemistry 66 9867840
2005 The histone H1 C-terminal domain binds to the apoptotic nuclease, DNA fragmentation factor (DFF40/CAD) and stimulates DNA cleavage. Biochemistry 56 15910001
2001 Apoptosis induction by T-2 toxin: activation of caspase-9, caspase-3, and DFF-40/CAD through cytosolic release of cytochrome c in HL-60 cells. Bioscience, biotechnology, and biochemistry 49 11577712
2001 Ionic and cofactor requirements for the activity of the apoptotic endonuclease DFF40/CAD. Molecular and cellular biochemistry 42 11330826
1999 Multiple domains of DFF45 bind synergistically to DFF40: roles of caspase cleavage and sequestration of activator domain of DFF40. Biochemical and biophysical research communications 34 10527861
1999 Study of DFF45 in its role of chaperone and inhibitor: two independent inhibitory domains of DFF40 nuclease activity. Biochemical and biophysical research communications 30 10527860
2017 Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation. Biochemical and biophysical research communications 28 28104392
2002 T and B leukemic cell lines exhibit different requirements for cell death: correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation and apoptosis in T cell lines but not in Burkitt's lymphoma. Leukemia 27 11960352
2012 Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease. The Journal of biological chemistry 25 22253444
2016 An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells. Neuro-oncology 20 26755073
2013 GM-CSF-DFF40: a novel humanized immunotoxin induces apoptosis in acute myeloid leukemia cells. Apoptosis : an international journal on programmed cell death 19 23529188
2013 Eradication of Human Ovarian Cancer Cells by Transgenic Expression of Recombinant DNASE1, DNASE1L3, DNASE2, and DFFB Controlled by EGFR Promoter: Novel Strategy for Targeted Therapy of Cancer. Journal of genetic syndromes & gene therapy 19 24587967
2008 The major apoptotic endonuclease DFF40/CAD is a deoxyribose-specific and double-strand-specific enzyme. Apoptosis : an international journal on programmed cell death 18 18283539
2006 Unique features of the apoptotic endonuclease DFF40/CAD relative to micrococcal nuclease as a structural probe for chromatin. Biochemistry and cell biology = Biochimie et biologie cellulaire 18 16936813
2017 DNA fragmentation factors 40 and 45 (DFF40/DFF45) and B-cell lymphoma 2 (Bcl-2) protein are underexpressed in uterine leiomyosarcomas and may predict survival. OncoTargets and therapy 17 29075126
2005 Sulindac activates nuclear translocation of AIF, DFF40 and endonuclease G but not induces oligonucleosomal DNA fragmentation in HT-29 cells. Life sciences 17 15946692
2006 The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions. Apoptosis : an international journal on programmed cell death 16 16699957
2005 Attenuated expression of DFFB is a hallmark of oligodendrogliomas with 1p-allelic loss. Molecular cancer 16 16156899
2018 The tumor antagonistic steroidal alkaloid Solanidine prompts the intrinsic suicidal signal mediated DFF-40 nuclear import and nucleosomal disruption. Life sciences 13 29524520
2015 Sensitization of breast cancer cells to doxorubicin via stable cell line generation and overexpression of DFF40. Biochemistry and cell biology = Biochimie et biologie cellulaire 13 26529233
2008 High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40/CAD due to HMG-box interactions with DNA. Acta biochimica Polonica 12 18239742
2021 The role of the DFF40/CAD endonuclease in genomic stability. Apoptosis : an international journal on programmed cell death 10 33387146
2018 Endometrial Polyps and Benign Endometrial Hyperplasia Have Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 9 28914671
2010 Histone H1 subtype preferences of DFF40 and possible nuclear localization of DFF40/45 in normal and trichostatin A-treated NB4 leukemic cells. Apoptosis : an international journal on programmed cell death 9 19882353
2009 Fifty C-terminal amino acid residues are necessary for the chaperone activity of DFF45 but not for the inhibition of DFF40. BMB reports 9 19944011
2013 Safeguarding Stem Cell-Based Regenerative Therapy against Iatrogenic Cancerogenesis: Transgenic Expression of DNASE1, DNASE1L3, DNASE2, DFFB Controlled By POLA1 Promoter in Proliferating and Directed Differentiation Resisting Human Autologous Pluripotent Induced Stem Cells Leads to their Death. Journal of stem cell research & therapy 8 25045589
2021 DFF40-iRGD, a novel chimeric protein with efficient cytotoxic and apoptotic effects against triple-negative breast cancer cells. Biotechnology letters 7 34482510
2021 DFF40 deficiency in cancerous T cells is implicated in chemotherapy drug sensitivity and resistance through the regulation of the apoptotic pathway. Biochemical pharmacology 6 34678222
2023 MEG3 Regulates CSE-Induced Apoptosis by Regulating miR-421/DFFB Signal Axis. International journal of chronic obstructive pulmonary disease 5 37215747
2022 Molecular basis of apoptotic DNA fragmentation by DFF40. Cell death & disease 5 35236824
2020 HNRNPCL1, PRAMEF1, CFAP74, and DFFB: Common Potential Biomarkers for Sporadic and Suspected Lynch Syndrome Endometrial Cancer. Cancer management and research 5 33177874
2022 Malignant DFFB isoform switching promotes leukemia survival in relapse pediatric T-cell acute lymphoblastic leukemia. EJHaem 4 36819185
2021 Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells. Cancers 4 34771741
2012 [Repressional effects of the glutamate antibodies on expression of Dffb gene in the brain of rats with experimental Alzheimer's disease]. Molekuliarnaia biologiia 3 23156675
2019 Two Simple Methods for Optimizing the Production of "Difficult-to-Express" GnRH-DFF40 Chimeric Protein. Advanced pharmaceutical bulletin 2 31592077
2025 DFFB suppresses interferon to enable cancer persister cell regrowth. bioRxiv : the preprint server for biology 1 40894800
2022 Energetic metabolic reprogramming in Jurkat DFF40-deficient cancer cells. Molecular and cellular biochemistry 1 35460011
2006 Generation of aberrant forms of DFF40 concurrent with caspase-3 activation during acute and chronic liver injury in rats. Biochemical and biophysical research communications 1 17011520

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