Affinage

DFFA

DNA fragmentation factor subunit alpha · UniProt O00273

Length
331 aa
Mass
36.5 kDa
Annotated
2026-06-09
94 papers in source corpus 23 papers cited in narrative 21 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DFFA (DFF45/ICAD) is the dedicated regulatory subunit of the apoptotic DNA-fragmentation machinery, functioning as both a folding chaperone and a direct inhibitor of the nuclease DFF40/CAD that executes internucleosomal DNA degradation during programmed cell death (PMID:9422506, PMID:9560346). The long isoform ICAD-L acts as a specific chaperone that is required during CAD synthesis to produce soluble, functional nuclease, an activity the short isoform ICAD-S largely lacks (PMID:10336474); structurally, the C-terminal domain of DFF45 adopts a four-helix fold with a negatively charged surface that complements the catalytic domain of DFF40, and the N-terminal domains of the two proteins fold cooperatively upon heterodimerization in a mutual-chaperoning mechanism (PMID:11371636, PMID:12144788). DFF45 holds CAD inactive through multiple independent domains that sequester the activator region and block the catalytic center, with chaperone and inhibitory activities separable to distinct regions of the protein (PMID:10409614, PMID:10527861, PMID:10527860, PMID:19944011). The DFF45/CAD complex resides predominantly in the nucleus, directed by a bipartite NLS in ICAD-L that ICAD-S lacks (PMID:10908575, PMID:10694446). Apoptotic signaling triggers caspase-3 cleavage of DFF45, with the C-terminal cleavage event being essential to dissociate the inhibitor and release active CAD, which then fragments chromosomal DNA into nucleosomal ladders (PMID:9422506, PMID:9786842); caspase-2 can also cleave ICAD and activate the pathway (PMID:17945178). Acute depletion or caspase-mediated loss of ICAD is sufficient to activate CAD and drive apoptosis through a positive-feedback caspase loop (PMID:17616520, PMID:25248749), and ICAD deficiency confers resistance to genotoxic apoptosis while promoting genomic instability and tumorigenesis (PMID:23451280). The chaperone/inhibitor mechanism is conserved, with Drosophila DREP-1 serving as the functional ICAD homolog (PMID:10781612).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Established the founding dual identity of DFFA: how the apoptotic DNase is held inactive and then unleashed, defining ICAD as both chaperone and inhibitor of CAD.

    Evidence Biochemical purification from mouse lymphoma, recombinant reconstitution in COS cells and cell-free systems, caspase-3 cleavage and DNase assays; independently confirmed for the human CPAN/CAD homolog from Jurkat cells

    PMID:9422506 PMID:9560346

    Open questions at the time
    • Domain basis of inhibition versus chaperoning not yet resolved
    • In vivo physiological relevance untested at this stage
  2. 1998 Medium

    Resolved which proteolytic event matters: pinpointed caspase-3 cleavage of the DFF45 C-terminus as the essential activating step, distinguishing it from non-activating N-terminal cleavage.

    Evidence Apoptosis induction in caspase-3-deficient versus caspase-3-reconstituted MCF-7 cells with Western blot cleavage analysis

    PMID:9786842

    Open questions at the time
    • Single lab; identity of the N-terminal-cleaving caspase not defined
    • Quantitative contribution of each site to release kinetics unknown
  3. 1998 Medium

    Localized the inhibitor and complex to the nucleus, countering a presumed cytoplasmic anchoring role and constraining models of where DNA fragmentation is regulated.

    Evidence GFP-ICAD live imaging across human, pig and chicken cells plus co-fractionation with topoisomerase I

    PMID:9743604

    Open questions at the time
    • NLS not yet mapped
    • Mechanism of nuclear retention versus import undefined
  4. 1999 High

    Dissected the molecular logic of inhibition and isoform divergence, showing distinct DFF45 domains sequester CAD's activator and catalytic regions and that the short isoform inhibits but cannot chaperone.

    Evidence Systematic deletion mutagenesis, recombinant reconstitution and binding/inhibition assays; Sf9 and cell-free chaperone reconstitution comparing ICAD-L and ICAD-S

    PMID:10336474 PMID:10409614 PMID:10527860 PMID:10527861

    Open questions at the time
    • Atomic-level interaction surfaces not yet resolved
    • Why ICAD-S retains inhibition but loses chaperoning unexplained structurally
  5. 2000 High

    Defined the nuclear-targeting determinants, mapping an autonomous bipartite NLS in ICAD-L that ICAD-S lacks and showing additive targeting by ICAD and CAD signals.

    Evidence GFP fusions, deletional mutagenesis, immunofluorescence and fractionation in HeLa and MCF7, with caspase-3-dependent nuclear ICAD loss; complementary GFP NLS mapping

    PMID:10694446 PMID:10908575

    Open questions at the time
    • Functional consequence of cytoplasmic ICAD-S not fully defined
    • Import receptor recognizing the NLS not identified
  6. 2001 High

    Provided the structural basis of mutual chaperoning, showing the unstructured DFF45 N-terminal domain folds only upon binding the DFF40 N-terminal domain.

    Evidence NMR solution structure of the DFF40/DFF45 NTD heterodimer

    PMID:11371636

    Open questions at the time
    • Structure of the catalytic-domain inhibitory contacts not covered
    • Dynamics of cleavage-induced dissociation not captured
  7. 2001 Medium

    Tested the in vivo necessity of DFFA for DNA fragmentation, revealing both DFF45-dependent and DFF45-independent endonuclease pathways in neurons.

    Evidence DFF45 knockout mice in a traumatic brain injury model and primary neuronal cultures with stimulus-specific DNA laddering assays

    PMID:11471558

    Open questions at the time
    • Identity of the DFF45-independent endonucleases unknown
    • Negative/partial phenotype limits mechanistic conclusions
  8. 2002 High

    Explained the structural origin of chaperone activity and its loss in the short isoform, attributing chaperoning to a charge-complementary C-terminal four-helix domain.

    Evidence NMR solution structure of the DFF-C domain of DFF45; reconstitution of CAD/ICAD-S complexes in E. coli and mammalian cells with activity and localization assays

    PMID:12136086 PMID:12144788

    Open questions at the time
    • Direct structure of the chaperone-substrate intermediate not determined
    • Quantitative chaperone efficiency differences not structurally explained in full
  9. 2007 High

    Extended the activating protease repertoire and established ICAD as the sole functional CAD inhibitor genetically, while showing CAD activation feeds a positive caspase loop.

    Evidence Cell-permeable caspase-2 delivery with in vitro cleavage and DNA fragmentation; DT40 knockout complementation with ICAD-L/ICAD-S and TEV-cleavable constructs

    PMID:17616520 PMID:17945178

    Open questions at the time
    • Relative physiological contribution of caspase-2 versus caspase-3 unquantified
    • Molecular mediators of the positive-feedback loop undefined
  10. 2009 Medium

    Formally separated chaperone from inhibitory function within DFF45 by mapping a C-terminal segment required for chaperoning but dispensable for inhibition.

    Evidence Limited proteolysis, truncation mutagenesis and biochemical activity assays

    PMID:19944011

    Open questions at the time
    • Single in vitro study
    • Cellular consequence of the separation-of-function mutant untested
  11. 2012 Medium

    Refined the inhibitory mechanism and connected DFFA to upstream splicing control, showing ICAD peptides block CAD dimerization and active site, and that SRSF1-dependent splicing of ICAD governs apoptotic outcome.

    Evidence SPOT peptide array and soluble inhibition assays for the mechanism; Pnn knockdown, splice-specific RT-PCR and SRSF1 rescue for splicing control

    PMID:22454513 PMID:22727028

    Open questions at the time
    • Peptide-based inhibition lacks structural validation
    • Whether SRSF1-driven ICAD splicing operates beyond MCF-7 unknown
  12. 2014 High

    Demonstrated causal sufficiency: acute loss of ICAD alone activates CAD and triggers apoptosis through caspase feedback, formalizing ICAD as the constitutive brake on cell death.

    Evidence Auxin-inducible degron depletion of ICAD with flow cytometry and apoptotic-marker readouts in DT40 and yeast

    PMID:25248749

    Open questions at the time
    • Trigger linking initial CAD activity to caspase amplification not molecularly defined
    • Generality across mammalian tissues not tested
  13. 2013 Medium

    Tied DFFA function to genome integrity and disease, showing ICAD loss causes apoptosis resistance, genomic instability and increased tumorigenesis.

    Evidence ICAD knockout mice in a dimethylhydrazine colon tumorigenesis model with array CGH and apoptosis/PARP-1 assays

    PMID:23451280

    Open questions at the time
    • Mechanistic link between DNase regulation and chromosomal aberrations not fully resolved
    • Human tumor relevance not established here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DFFA-controlled CAD release is precisely coupled to caspase amplification, and the identity of DFF45-independent endonucleases that operate in parallel, remain unresolved.
  • Molecular components of the CAD-driven positive-feedback caspase loop unidentified
  • DFF45-independent fragmentation nucleases uncharacterized
  • Structural intermediate of caspase cleavage-induced dissociation not captured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 4 GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-5357801 Programmed Cell Death 3
Partners
DFFB
Complex memberships
DFF (DFF40/DFF45 heterodimer)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ICAD (DFF45) functions as both an inhibitor and a chaperone for CAD (DFF40): during synthesis ICAD complexes with CAD to keep it inactive; caspase-3 cleavage of ICAD releases CAD DNase activity, which then translocates to the nucleus and degrades chromosomal DNA into nucleosomal fragments. Biochemical purification from mouse lymphoma cells, recombinant protein expression in COS cells and cell-free system, in vitro DNase activity assays, caspase-3 cleavage assays Nature High 9422506
1998 Human DFF45 (ICAD) is required for the expression and stabilization of the human caspase-activated nuclease CPAN (human CAD homolog) in an inactive state in living cells; proteolytic cleavage of DFF45 by caspases in vitro dissociates DFF45 fragments from CPAN and activates its endonuclease activity. Protein purification and cDNA cloning from Jurkat cells, recombinant protein expression, in vitro caspase cleavage, endonuclease activity assays Current biology : CB High 9560346
1998 DFF45/ICAD cleavage during apoptosis requires caspase-3 for the C-terminal cleavage event that activates the DNase; cleavage of the N-terminal region by another caspase alone (in the absence of caspase-3) leaves the DFF45 enzyme inactive, establishing that caspase-3 cleavage of the C-terminal region is essential for activation. Apoptosis induction in MCF-7 cells lacking functional caspase-3 vs. MCF-7 cells expressing caspase-3; Western blot analysis of DFF45 cleavage The Journal of biological chemistry Medium 9786842
1999 ICAD-L (long form) functions as a specific chaperone for CAD, facilitating its correct folding during synthesis; ICAD-S (short form) cannot serve as a chaperone. CAD expressed alone in Sf9 cells is insoluble, but co-expression with ICAD-L yields soluble, functional CAD. In vitro translation of CAD without ICAD-L produces non-functional protein, whereas addition of ICAD-L rescues synthesis of functional CAD. Sf9 baculovirus co-expression system, in vitro transcription/translation, fractionation, recombinant protein purification, DNase activity assays The Journal of biological chemistry High 10336474
2000 Endogenous and heterologously expressed ICAD (DFF45) and CAD reside predominantly in the nucleus in non-apoptotic cells, not in the cytoplasm. Deletional mutagenesis identified a bipartite nuclear localization signal (NLS) in ICAD; ICAD-S lacks this NLS. The two NLSs (in ICAD and CAD) have an additive effect on nuclear targeting of the CAD-ICAD complex. Staurosporine-induced apoptosis causes caspase-3-dependent proteolysis and disappearance of ICAD from nuclei. GFP fusion proteins, deletional mutagenesis, immunoblotting, immunofluorescence microscopy, subcellular fractionation, HeLa and MCF7 cells The Journal of cell biology High 10908575
1998 GFP-ICAD fusion protein is nuclear (not cytoplasmic) in healthy human, pig, and chicken cells; endogenous ICAD co-fractionates with nuclear marker DNA topoisomerase I. This argues against a cytoplasmic anchoring function for ICAD. GFP fusion protein live imaging, subcellular fractionation, immunoblotting Experimental cell research Medium 9743604
2001 Solution structure of the heterodimeric complex between the N-terminal domains (NTDs) of DFF40 and DFF45 was determined by NMR. The NTD of DFF45 alone is unstructured in solution; its folding is induced upon binding to the DFF40 NTD. The complex reveals an extensive network of intermolecular interactions burying a hydrophobic cluster, supporting a mutual chaperoning mechanism. NMR spectroscopy, solution structure determination Proceedings of the National Academy of Sciences of the United States of America High 11371636
1999 DFF45 inhibits DFF40 nuclease activity through multiple independent domains: domain D1 sequesters the activator domain of DFF40, domain D2 blocks the catalytic domain. Caspase cleavage of DFF45 disrupts synergistic binding of these domains to DFF40, releasing active nuclease. DFF35 (short isoform) cannot act as a chaperone but binds DFF40 strongly and inhibits its nuclease activity. Deletion mutagenesis, recombinant protein expression, functional inhibition assays, binding analysis The Journal of biological chemistry High 10409614 10527860 10527861
2002 Solution structure of the C-terminal domain (DFF-C) of DFF45/ICAD was determined by NMR. DFF-C consists of four alpha-helices in a novel packing arrangement with a large cluster of negatively charged residues, suggesting charge complementation with the positively charged catalytic domain of DFF40 underlies chaperone activity. DFF35 lacks chaperone activity because its sequence is truncated within the second alpha-helix, disrupting both the hydrophobic core and the negative charge cluster. NMR solution structure determination Journal of molecular biology High 12144788
2000 ICAD-L is nuclear due to an autonomous NLS located in its C-terminal 20 amino acids. ICAD-S lacks this NLS (replaced by 4 different amino acids through alternative splicing) and is distributed throughout the cell. GFP:CAD fusion protein is also nuclear in transfected cells. GFP fusion proteins, mutational analysis, transfected cell imaging Experimental cell research Medium 10694446
1998 Recombinant human DFF45/ICAD substitutes for healthy cell cytosol in inhibiting nuclear DNA fragmentation activity, and cytosols immunodepleted of DFF45 lose this inhibitory activity, establishing DFF45 as the principal inhibitor of apoptotic DNase activity in healthy cell cytosol. Cell-free DNA fragmentation assay, recombinant protein complementation, immunoadsorption depletion, immunoblotting Biochemical and biophysical research communications Medium 9875236
2000 Drosophila DREP-1 is the functional homolog of ICAD (dICAD): it inhibits Drosophila CAD (dCAD) DNase, is cleaved at a specific site by human caspase-3 and by extracts from apoptotic S2 cells, and is complexed with dCAD in proliferating cells. Expression of caspase-resistant dICAD/DREP-1 in Drosophila neuronal cells prevents apoptotic DNA fragmentation. Recombinant protein inhibition assays, immunoprecipitation, caspase cleavage assays, caspase-resistant mutant expression, immunohistochemistry, Northern hybridization The Journal of biological chemistry High 10781612
2007 Caspase-2 cleaves DFF45/ICAD both in vitro and inside cells (demonstrated by cell-permeable Tat-reverse-caspase-2 delivery), inducing nuclear DNA fragmentation, establishing caspase-2 as a writer for ICAD cleavage and activation of the CAD pathway. Cell-permeable caspase-2 delivery, in vitro cleavage assay, DNA fragmentation analysis, caspase activity assays Archives of biochemistry and biophysics Medium 17945178
2007 DFF45 genetic analysis in chicken DT40 cells: ICAD-S cannot replace ICAD-L as a chaperone for producing active CAD in vivo, but caspase-resistant ICAD-S (TEV cleavage sites substituted) can inhibit CAD activation upon apoptosis induction. ICAD appears to be the only functional inhibitor of CAD activation in cell-free extracts. CAD activation drives apoptosis through a positive feedback loop via caspase activation. DT40 gene knockout, human ICAD-L/ICAD-S expression in double knock-out cells, TEV-cleavable ICAD constructs, apoptosis assays The Journal of biological chemistry High 17616520
2014 Auxin-induced rapid degradation of ICAD using the auxin-inducible degron (AID) system directly activates CAD and is sufficient to induce cell death in DT40 and yeast cells, triggering caspase activation and classical apoptotic hallmarks (phosphatidylserine exposure, nuclear fragmentation) in vertebrate cells, demonstrating that CAD activation drives apoptosis through a positive feedback loop. Auxin-inducible degron system, flow cytometry, apoptosis assays in DT40 and yeast cells The Journal of biological chemistry High 25248749
2002 Co-expression of murine CAD with ICAD-S in E. coli or mammalian cells produces a functional DFF complex whose caspase-3 activation releases active DNase. ICAD-S chaperone activity is 1-2 orders of magnitude less effective than ICAD-L. Co-expression of ICAD-S (which lacks an NLS) leads to homogeneous intracellular distribution of CAD, while ICAD-L variants lacking the NLS exclude EGFP-CAD from nuclei in ~50% of cells, establishing the NLS of ICAD-L as critical for nuclear accumulation of the complex. E. coli and mammalian cell co-expression, EGFP fusion proteins, subcellular localization imaging, caspase-3 cleavage activity assays Nucleic acids research Medium 12136086
2001 DFF45 knockout mice display oligonucleosomal DNA fragmentation after traumatic brain injury (albeit delayed), indicating that DFF45-independent endonucleases contribute to DNA fragmentation in adult brain neurons. Primary neuronal cultures from DFF45 knockouts fail to show DNA laddering with staurosporine but retain DNA fragmentation with etoposide, distinguishing DFF45-dependent from DFF45-independent pathways. DFF45 knockout mice, controlled cortical impact TBI model, in vitro reconstitution, primary neuronal cultures, DNA fragmentation assays Molecular medicine (Cambridge, Mass.) Medium 11471558
2009 The C-terminal 50 amino acid residues (residues 281-300) of DFF45 are necessary for its chaperone activity but not for inhibition of DFF40 nuclease activity, establishing functional separation between these two activities within DFF45. Limited proteolysis, truncation mutagenesis, biochemical activity assays BMB reports Medium 19944011
2012 ICAD-derived peptides that interact with the dimerization (C2) domain and the catalytic centre (C3 domain) of CAD can inhibit CAD activity in solution, suggesting a dual inhibitory mechanism: prevention of CAD homodimerization and blockage of the active site. SPOT peptide array, soluble peptide inhibition assays, CAD activity measurements The FEBS journal Medium 22727028
2012 Loss of the splicing regulator Pnn (Pinin) in MCF-7 cells causes altered alternative splicing of ICAD, mediated by SRSF1, leading to cellular apoptosis; overexpression of SRSF1 restores normal ICAD splicing and rescues cells from apoptosis, placing SRSF1 upstream of ICAD in this pathway. RNA interference (Pnn knockdown), RT-PCR splicing analysis, SRSF1 overexpression rescue, apoptosis assays Journal of cell science Medium 22454513
2013 ICAD deficiency in colon epithelial cells confers resistance to apoptosis induced by genotoxic stress and is associated with severe genomic instability (amplifications and deletions) and increased colon tumorigenesis in mice, establishing ICAD as a component linking apoptosis and genomic stability maintenance. ICAD knockout mice, dimethylhydrazine-induced colon tumorigenesis model, array comparative genomic hybridization, in vitro apoptosis assays, PARP-1 activation assays PloS one Medium 23451280

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 2634 9422506
1998 CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45. Current biology : CB 190 9560346
2005 A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity. Diabetes 156 15919794
1998 Cleavage of DFF-45/ICAD by multiple caspases is essential for its function during apoptosis. The Journal of biological chemistry 146 9786842
2003 Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family. The Biochemical journal 103 12429024
1999 Functional differences of two forms of the inhibitor of caspase-activated DNase, ICAD-L, and ICAD-S. The Journal of biological chemistry 90 10336474
2000 Determinants of the nuclear localization of the heterodimeric DNA fragmentation factor (ICAD/CAD). The Journal of cell biology 78 10908575
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
2010 MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network. Molecular cancer 71 20687965
2012 Opposing roles of cell death-inducing DFF45-like effector B and perilipin 2 in controlling hepatic VLDL lipidation. Journal of lipid research 52 22661308
1998 ICAD/DFF regulator of apoptotic nuclease is nuclear. Experimental cell research 49 9743604
2011 Loss of mitogen-activated protein kinase phosphatase-1 protects from hepatic steatosis by repression of cell death-inducing DNA fragmentation factor A (DFFA)-like effector C (CIDEC)/fat-specific protein 27. The Journal of biological chemistry 48 21521693
2008 Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism. Metabolism: clinical and experimental 47 18702959
2003 dffA gene from Aspergillus oryzae encodes L-ornithine N5-oxygenase and is indispensable for deferriferrichrysin biosynthesis. Journal of bioscience and bioengineering 46 16233371
1998 Inhibition of apoptosis-associated DNA fragmentation activity in nonapoptotic cells: the role of DNA fragmentation factor-45 (DFF45/ICAD). Biochemical and biophysical research communications 43 9875236
2018 High expression of cell death-inducing DFFA-like effector a (CIDEA) promotes milk fat content in dairy cows with clinical ketosis. Journal of dairy science 41 30594378
2000 Identification and developmental expression of inhibitor of caspase-activated DNase (ICAD) in Drosophila melanogaster. The Journal of biological chemistry 40 10781612
2002 Growth phase-dependent expression of ICAD-L/DFF45 modulates the pattern of apoptosis in human colonic cancer cells. Cancer research 38 11929840
2009 Hepatic expression of cell death-inducing DFFA-like effector C in obese subjects is reduced by marked weight loss. Obesity (Silver Spring, Md.) 37 19661960
2010 Cell death-inducing DFF45-like effector, a lipid droplet-associated protein, might be involved in the differentiation of human adipocytes. The FEBS journal 36 20945533
2007 CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1/Sp3 binding. Nucleic acids research 36 18033804
2004 Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway. Acta pharmacologica Sinica 36 15132839
1998 Cytosolic nuclease activated by caspase-3 and inhibited by DFF-45. Biochemical and biophysical research communications 36 9480834
2017 Evaluation of miRNA-196a2 and apoptosis-related target genes: ANXA1, DFFA and PDCD4 expression in gastrointestinal cancer patients: A pilot study. PloS one 35 29091952
2010 A physiological role for fat specific protein 27/cell death-inducing DFF45-like effector C in adipose and liver. Biological & pharmaceutical bulletin 34 20190390
2002 Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours. British journal of cancer 34 11870543
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
2000 Differential localization of ICAD-L and ICAD-S in cells due to removal of a C-terminal NLS from ICAD-L by alternative splicing. Experimental cell research 33 10694446
2012 Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICAD. Journal of cell science 32 22454513
2002 Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation. Journal of molecular biology 32 12144788
2010 Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) stimulates VLDL assembly through activation of cell death-inducing DFFA-like effector B (CideB). The Journal of biological chemistry 30 20551328
2007 Evaluation of biofilm production and prevalence of the icaD gene in methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains isolated from patients with nosocomial infections and carriers. FEMS immunology and medical microbiology 30 17537178
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
2014 Cell death-inducing DFFA-like effector b is required for hepatitis C virus entry into hepatocytes. Journal of virology 29 24829338
2002 Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes. American journal of physiology. Heart and circulatory physiology 28 12181128
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
2000 Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8 and caspase-3 in human lymphomas. The Journal of pathology 27 11004695
1999 Structure and promoter analysis of murine CAD and ICAD genes. Cell death and differentiation 27 10467348
2014 Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death: a cell suicide module. The Journal of biological chemistry 24 25248749
2013 Staphylococcus epidermidis with the icaA⁻/icaD⁻/IS256⁻ genotype and protein or protein/extracellular-DNA biofilm is frequent in ocular infections. Journal of medical microbiology 24 23861297
2008 GCN5 and BCR signalling collaborate to induce pre-mature B cell apoptosis through depletion of ICAD and IAP2 and activation of caspase activities. Gene 23 18538956
2001 Presence of DNA fragmentation and lack of neuroprotective effect in DFF45 knockout mice subjected to traumatic brain injury. Molecular medicine (Cambridge, Mass.) 22 11471558
2014 Minocycline inhibits ICAD degradation and the NF-κB activation induced by 6-OHDA in PC12 cells. Brain research 20 25195972
2007 Poly(ADP-ribose) polymerase (PARP) and DNA-fragmentation factor (DFF45): expression and correlation in normal, hyperplastic and neoplastic endometrial tissues. Pathology, research and practice 19 17258405
2006 Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene. The Biochemical journal 19 16248853
2001 DNA fragmentation factor 45 (DFF45) gene at 1p36.2 is homozygously deleted and encodes variant transcripts in neuroblastoma cell line. Neoplasia (New York, N.Y.) 19 11420752
2004 Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors. International journal of oncology 18 15492818
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
2016 Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A. Scientific reports 17 27282740
2013 Analysis of S. Epidermidis icaA and icaD genes by polymerase chain reaction and slime production: a case control study. BMC infectious diseases 17 23705749
2002 Imidazole-induced cell death, associated with intracellular acidification, caspase-3 activation, DFF-45 cleavage, but not oligonucleosomal DNA fragmentation. Apoptosis : an international journal on programmed cell death 17 12370494
2007 Caspase-2 cleaves DNA fragmentation factor (DFF45)/inhibitor of caspase-activated DNase (ICAD). Archives of biochemistry and biophysics 16 17945178
2006 The analysis of RCAS1 and DFF-45 expression in nasal polyps with respect to immune cells infiltration. BMC immunology 16 16551346
2017 Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors. The Journal of general virology 13 28745269
2012 Cell death-inducing DFF45-like effector b (Cideb) is present in pancreatic beta-cells and involved in palmitate induced beta-cell apoptosis. Diabetes/metabolism research and reviews 13 21948526
2009 Expression of apoptotic tumour necrosis factor receptor-associated factor, caspase recruitment domain and cell death-inducing DFF-45 effector genes in therapy-treated renal cell carcinoma. Nephrology (Carlton, Vic.) 13 19076291
2013 ICAD deficiency in human colon cancer and predisposition to colon tumorigenesis: linkage to apoptosis resistance and genomic instability. PloS one 12 23451280
2007 Genetic analysis of the short splice variant of the inhibitor of caspase-activated DNase (ICAD-S) in chicken DT40 cells. The Journal of biological chemistry 12 17616520
2002 The effect of ICAD-S on the formation and intracellular distribution of a nucleolytically active caspase-activated DNase. Nucleic acids research 11 12136086
2021 Cell death-inducing DFFA-like effector C/CIDEC gene silencing alleviates diabetic cardiomyopathy via upregulating AMPKa phosphorylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 33913563
2019 Frequency of icaA and icaD determinants and biofilm formation among coagulase-negative staphylococci associated with nasal carriage in neonatal intensive care units. Germs 10 31341833
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
2011 Human cell-death-inducing DFF45-like effector C induces apoptosis via caspase-8. Acta biochimica et biophysica Sinica 9 21865223
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
2001 Expression of ICAD-l and ICAD-S in human brain tumor and its cleavage upon activation of apoptosis by anti-Fas antibody. Japanese journal of cancer research : Gann 9 11473733
2017 Cell death-inducing DFF45-like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model. Journal of diabetes investigation 8 29078040
2014 Investigating the antiviral role of cell death-inducing DFF45-like effector B in HCV replication. The FEBS journal 7 24980280
2009 DFF45 expression in ovarian endometriomas. European journal of obstetrics, gynecology, and reproductive biology 7 19535198
2007 DFF45/ICAD restores cisplatin-induced nuclear fragmentation but not DNA cleavage in DFF45-deficient neuroblastoma cells. Oncogene 7 17353905
2013 siRNA-mediated knock-down of DFF45 amplifies doxorubicin therapeutic effects in breast cancer cells. Cellular oncology (Dordrecht, Netherlands) 6 24277473
2019 Daunorubicin can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation. Cancer drug resistance (Alhambra, Calif.) 5 35582720
2013 Cell death-inducing DFFA-like effector c (CIDEC/Fsp27) gene: molecular cloning, sequence characterization, tissue distribution and polymorphisms in Chinese cattles. Molecular biology reports 5 24065549
2012 Identification of ICAD-derived peptides capable of inhibiting caspase-activated DNase. The FEBS journal 5 22727028
2016 Hepatitis C Virus-Induced Degradation of Cell Death-Inducing DFFA-Like Effector B Leads to Hepatic Lipid Dysregulation. Journal of virology 4 26865724
2012 DFF45 expression in human endometrium is associated with menstrual cycle phases and decreases after menopause. Gynecologic and obstetric investigation 4 22378161
2008 Isolation of industrial strains of Aspergillus oryzae lacking ferrichrysin by disruption of the dffA gene. Journal of bioscience and bioengineering 4 19111645
2007 The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases. Folia histochemica et cytobiologica 4 18292826
2025 Cell death-inducing DNA fragmentation factor alpha (DFFA)-like effectors (CIDEs) improve lipid droplet (LD) formation and oil accumulation in plant tissues. Plant biotechnology journal 3 40488597
2018 MiRNA-145 Induces Apoptosis in a Gallbladder Carcinoma Cell Line by Targeting DFF45. Open life sciences 3 33817087
2017 Effects of cell death-inducing DFF45-like effector B on meat quality traits in Berkshire pigs. Genetics and molecular research : GMR 3 28549200
2006 Cell death-inducing DFF45-like effector may take part in neuronal apoptosis of the lumbar spinal cord after sciatic nerve injury caused by a firearm. Military medicine 3 16933827
2003 Expression, purification, crystallization of fragments from the C-terminal region of DFF45/ICAD. Acta crystallographica. Section D, Biological crystallography 3 12832800
2025 Cell death-inducing DFF45-like effector C intervenes the progression of nonsmall-cell lung cancer via modulating lipid metabolism. International journal of surgery (London, England) 2 40552859
2024 Evaluation of icaA and icaD Genes Involved in Biofilm Formation in Staphylococcus aureus Isolates from Clinical Sources Using Reverse Transcriptase PCR. Archives of Razi Institute 2 40599458
2016 Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma - Tissue Microarray of Human Samples. Journal of kidney cancer and VHL 2 28326275
2014 [Biofilm and role of icaA, icaD, and accumulation-associated protein in Staphylococcus epidermidis isolated in breast surgery]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 2 24796203
2004 CAD-ICAD complex structure derived from saturation transfer experiment and simulated annealing without using pairwise NOE information. Journal of molecular recognition : JMR 2 14872536
2023 Evaluation of anti-biofilm activity of Lactobacillus rhamnosus GG and Nisin on the expression of aap, ica-A and ica-D as biofilm-associated genes of Staphylococcus epidermidis. Iranian journal of microbiology 1 38045711
2001 Recombinant Human DFF45 Inhibits Apoptosis-specific Endonuclease in a Cell-free System of Xenopus Egg Extracts. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 1 12053194
2025 Biofilm Formation and Antibiotic Resistance in Orthopaedic Implant Infections: A Molecular Analysis of icaA, icaD, and mecA Genes in an Indian Cohort. Indian journal of orthopaedics 0 41541020
2025 Recurrent Intracranial Atherosclerotic Disease (ICAD)-Large-Vessel Occlusion (LVO) in Acute Lymphoblastic Leukemia Treated by Rescue Angioplasty: A Case Report. Cureus 0 41607956
2021 Effect of Ultraviolet Light on the Expression of icaD Gene in Staphylococcus aureus Local Isolates in Iraq. Archives of Razi Institute 0 35355742
2003 Crystallization of the N-terminal domain of DFF45: the mutual chaperone mechanism is challenged. Protein and peptide letters 0 12678820

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