Property Summary

NCBI Gene PubMed Count 53
PubMed Score 58.05
PubTator Score 136.56

Knowledge Summary


No data available


  Disease (1)

Disease Target Count P-value
osteosarcoma 7933 1.5e-06
psoriasis 6685 8.0e-05
Pick disease 1893 1.0e-04
lung cancer 4473 6.6e-03
group 3 medulloblastoma 2254 2.7e-02


  Differential Expression (5)

Disease log2 FC p
psoriasis -1.700 8.0e-05
osteosarcoma -2.210 1.5e-06
lung cancer 1.100 6.6e-03
group 3 medulloblastoma 1.200 2.7e-02
Pick disease -1.100 1.0e-04

Protein-protein Interaction (10)

Gene RIF (33)

26529233 Data suggest DFF40 expression in breast cancer cell line is involved in drug sensitivity/resistance to doxorubicin; apoptotic cell death due to doxorubicin (a topoisomerase II inhibitor) is enhanced by DFF40 overexpression in breast cancer cell line.
26106156 Data show that the caspase-activated DNase (CAD) is activated when caspases cleave its endogenous inhibitor ICAD, resulting in the characteristic DNA laddering of apoptosis.
25086620 Combinatorial use of some sulfonamides such as acetazolamide along with increased expression of DFF40 can potently kill tumor cells via apoptosis.
24838313 DFF40/CAD-independent mechanism driving conformational nuclear changes during caspase-dependent cell death
23430749 the highest order of chromatin compaction observed in the later steps of caspase-dependent apoptosis relies on DFF40/CAD-mediated DNA damage by generating 3'-OH ends in single-strand rather than double-strand DNA nicks/breaks
23229555 These results suggest a cooperative activity between CAD and DNAS1L3 to accomplish internucleosomal DNA fragmentation .
22609799 Human papillomavirus type 16 E6 protein inhibits DNA fragmentation via interaction with DNA fragmentation factor 40
22253444 the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation.
22023725 During apoptotic rearrangement of interchromatin granule clusters, the nuclear matrix (NuMa rearrangement) and chromatin are closely associated. This process occurs in defined stages and depends on the activity of protein phosphatases, caspases and CAD.
22011247 Data show that among the 13 SNPs in the 3 genes, only 3 were found to be polymorphic: R196K and K277R in the DFFB gene, and S12L in the EndoG gene, and all 6 SNPs in the FEN-1 gene were entirely monoallelic.
21820410 These data suggest that DFF 40 mediated apoptosis plays a significant role in mediating sepsis induced cellular dysfunction.
20855536 Observational study of gene-disease association. (HuGE Navigator)
19882353 The heterodimer, DFF40-DFF45, is localized to the chromatin fraction under apoptotic as well as non-apoptotic conditions.
18283539 We have found that neither single-stranded DNA, single-stranded RNA, double-stranded RNA nor RNA-DNA heteroduplexes are cleaved by the DFF40/CAD nuclease.
18239742 changes induced in DNA conformation upon HMG-box binding makes the substrate more accessible to cleavage by DFF40/CAD nuclease and thus may contribute to preferential linker DNA cleavage during apoptosis
17938174 C-terminal region of each subunit, DFF40 (RLKRK) and DFF45 (KRAR), is essential for nuclear accumulation of the DFF complex.
17492772 Data suggest that erythroblast chromatin degradation may involve caspase activated DNase and apoptosis inducing factor, enzymes distinct from those active in apoptotic cells.
17239993 These results suggest that CAD is the endogenous endonuclease that mediates internucleosomal DNA degradation in rotenone-induced apoptosis.
16699957 poly-glutamic acid and heparin inhibit DFF40/CAD, the latter one being highly effective at nanomolar concentrations. The inhibitory poly-anions bind to the nuclease and impair its ability to bind double-stranded DNA.
16529748 CAD is downregulated at the mRNA and protein level during the erythroid differentiation in TF-1 cells.
16428311 the N-terminal region was found to be responsible for the requirement of salt for fibril formation
16204257 in apoptotic cells, endogenous and exogenous CAD forms limited oligomers, representing the active nuclease
16156899 DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development
16121124 levels of CAD were significantly higher in the nuclear fraction of temporal lobe epilepsy samples
16049016 AIF is responsible for stage I nuclear morphology and HMW DNA degradation is a caspase-activated DNase and AIF-independent process
16007181 Our findings of high frequency of Alu-mediated hCAD deletion in human hepatoma underscore the implication of hCAD in hepatocarcinogenesis
15910001 Interactions identified here between human placenta histone H1 carboxyl-terminal domain and DFF40/CAD target and activate linker DNA cleavage during the terminal stages of apoptosis.
15703174 PARP-1 poly(ADP-ribosyl)ation is a terminal event in the apoptotic response that occurs in response to DNA fragmentation and directly influences DFF40 activity
15569712 CAD involves unrestricted accessibility of chromosomal DNA at the initial phase of apoptosis, followed by its nuclear immobilization that may prevent the release of the active nuclease into the extracellular environment.
12748178 subunit structures and stoichiometries in human cells before and after induction of apoptosis
12738667 Hsp70 binds free CAD in TCR-stimulated T cells to stabilize and augment its activity.
12610505 Mutations and aberrantly spliced transcripts for the CAD gene are frequently associated with hepatocellular carcinoma.
12404116 HIV-1 protease directly cleaves and activates procaspase 8 in T cells, which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP

AA Sequence


Text Mined References (56)

PMID Year Title
26529233 2015 Sensitization of breast cancer cells to doxorubicin via stable cell line generation and overexpression of DFF40.
26106156 2015 Engineered cellular gene-replacement platform for selective and inducible proteolytic profiling.
25086620 2014 Stable overexpression of DNA fragmentation factor in T-47D cells: sensitization of breast cancer cells to apoptosis in response to acetazolamide and sulfabenzamide.
24838313 2014 Caspase-activated DNase is necessary and sufficient for oligonucleosomal DNA breakdown, but not for chromatin disassembly during caspase-dependent apoptosis of LN-18 glioblastoma cells.
23720494 2013 Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
23430749 2013 Chromatin collapse during caspase-dependent apoptotic cell death requires DNA fragmentation factor, 40-kDa subunit-/caspase-activated deoxyribonuclease-mediated 3'-OH single-strand DNA breaks.
23229555 2013 Apoptotic DNA fragmentation may be a cooperative activity between caspase-activated deoxyribonuclease and the poly(ADP-ribose) polymerase-regulated DNAS1L3, an endoplasmic reticulum-localized endonuclease that translocates to the nucleus during apoptosis.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22609799 2012 Human papillomavirus type 16 E6 protein inhibits DNA fragmentation via interaction with DNA fragmentation factor 40.
22253444 2012 Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease.
22023725 2012 Early apoptotic reorganization of spliceosomal proteins involves caspases, CAD and rearrangement of NuMA.
22011247 2012 Nonsynonymous single-nucleotide polymorphisms of the human apoptosis-related endonuclease--DNA fragmentation factor beta polypeptide, endonuclease G, and Flap endonuclease-1--genes show a low degree of genetic heterogeneity.
21820410 2011 Septic sera induces apoptosis and DNA fragmentation factor 40 activation in fibroblasts.
20855536 2010 Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma.
19882353 2010 Histone H1 subtype preferences of DFF40 and possible nuclear localization of DFF40/45 in normal and trichostatin A-treated NB4 leukemic cells.
18283539 2008 The major apoptotic endonuclease DFF40/CAD is a deoxyribose-specific and double-strand-specific enzyme.
18239742 2008 High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40/CAD due to HMG-box interactions with DNA.
17938174 2007 Sequence elements in both subunits of the DNA fragmentation factor are essential for its nuclear transport.
17492772 2007 The chromatin of differentiating erythroblasts is cleaved into large size fragments independent of caspase activated DNase and apoptosis inducing factor.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17239993 2007 RNAi knockdown of caspase-activated DNase inhibits rotenone-induced DNA fragmentation in HeLa cells.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16699957 2006 The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions.
16529748 2006 Erythropoietin activates caspase-3 and downregulates CAD during erythroid differentiation in TF-1 cells - a protection mechanism against DNA fragmentation.
16428311 2005 Identification of the region responsible for fibril formation in the CAD domain of caspase-activated DNase.
16204257 2005 Oligomerization state of the DNA fragmentation factor in normal and apoptotic cells.
16156899 2005 Attenuated expression of DFFB is a hallmark of oligodendrogliomas with 1p-allelic loss.
16121124 2006 Caspase-3 cleavage and nuclear localization of caspase-activated DNase in human temporal lobe epilepsy.
16049016 2005 The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated DNase to the nuclear phenotype and DNA degradation during apoptosis.
16007181 2005 High-frequency Alu-mediated genomic recombination/deletion within the caspase-activated DNase gene in human hepatoma.
15910001 2005 The histone H1 C-terminal domain binds to the apoptotic nuclease, DNA fragmentation factor (DFF40/CAD) and stimulates DNA cleavage.
15703174 2005 Modulation of DNA fragmentation factor 40 nuclease activity by poly(ADP-ribose) polymerase-1.
15572351 2005 Interaction of DNA fragmentation factor (DFF) with DNA reveals an unprecedented mechanism for nuclease inhibition and suggests that DFF can be activated in a DNA-bound state.
15569712 2004 Contrasting nuclear dynamics of the caspase-activated DNase (CAD) in dividing and apoptotic cells.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15149602 2004 Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway.
15147901 2004 Characterization of splice variants of human caspase-activated DNase with CIDE-N structure and function.
14759258 2004 An unappreciated role for RNA surveillance.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12748178 2003 Subunit structures and stoichiometries of human DNA fragmentation factor proteins before and after induction of apoptosis.
12738667 2003 Heat shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimulated T cells.
12610505 2003 Aberrant caspase-activated DNase (CAD) transcripts in human hepatoma cells.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11371636 2001 Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45.
10959840 2000 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution.
10932250 2000 Structure of the heterodimeric complex between CAD domains of CAD and ICAD.
10830907 2000 Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene.
10619428 1999 Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis.
10527861 1999 Multiple domains of DFF45 bind synergistically to DFF40: roles of caspase cleavage and sequestration of activator domain of DFF40.
10527860 1999 Study of DFF45 in its role of chaperone and inhibitor: two independent inhibitory domains of DFF40 nuclease activity.
10409614 1999 Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40.
9689044 1998 Molecular cloning and characterization of human caspase-activated DNase.
9671700 1998 The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis.
9560346 1998 CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45.
9422506 1998 A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD.
9108473 1997 DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis.