The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

DFFA  -  DNA fragmentation factor, 45kDa, alpha...

Homo sapiens

Synonyms: DFF-45, DFF1, DFF45, DNA fragmentation factor 45 kDa subunit, DNA fragmentation factor subunit alpha, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DFFA

  • Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours [1].
  • We have studied the presence and functional status of ICAD / DFF in human glioma cell lines [2].
  • The present findings suggest that primary brain tumors and normal brain constitutively express ICAD / DFF, and that there is a difference between the expression levels of ICAD-L and ICAD-S [2].
  • Several fragments from the C-terminal region of DFF45/ICAD have been cloned and expressed in Escherichia coli as His-tagged proteins [3].
  • RESULTS: DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion [4].

High impact information on DFFA


Chemical compound and disease context of DFFA


Biological context of DFFA


Anatomical context of DFFA

  • An antiserum against human DFF45 detected 44 and 34 kDa proteins (major and minor, respectively) in the cytosols but not in the nuclear or membrane fractions of various cultured human cells [16].
  • The chromosomal DNA in cells expressing caspase-resistant ICAD remained intact after treatment with staurosporine but their chromatin condensed as found in parental Jurkat cells [17].
  • Human T-cell lymphoma Jurkat cells, as well as their transformants expressing caspase-resistant ICAD, were treated with staurosporine [17].
  • To investigate the mechanism of FAS resistance, the expression of caspase-8 was analysed by immunohistochemistry, together with that of the substrates caspase-3 and ICAD, in 52 representative samples from non Hodgkin's lymphoma (NHL), 12 from Hodgkin's disease (HD), and eight benign lymphoid tissues [18].
  • Since ICAD is located in cell nuclei, it is unlikely that the protein functions primarily in the cytoplasm either as an anchor for CAD/CPAN or as a factor that enters the nucleus following caspase cleavage in order to activate resident endonucleases [19].

Associations of DFFA with chemical compounds


Regulatory relationships of DFFA

  • Purified DFF40 alone possesses intrinsic nuclease activity that is inhibited by its association with DFF45 [25].
  • We have assessed the contribution of apoptosis-inducing factor (AIF) and inhibitor of caspase-activated DNase (ICAD) to the nuclear morphology and DNA degradation pattern in staurosporine-induced apoptosis [26].
  • Curcumin-induced cleavage of PARP and DFF45 was inhibited by hsp70 but enhanced in Ashsp70 cells [27].

Other interactions of DFFA

  • We show that the CIDE-N of CIDE-B interacts with CIDE-N domains of both DFF40 and DFF45 [5].
  • In a cell-free assay, caspases-3, -6, -7, -8, and granzyme B initiated benzoyloxycarbonyl-Asp-Glu-Val-Asp (DEVD) cleaving caspase activity, DFF45/ICAD inactivation, and DNA fragmentation, but calpain and cathepsin D failed to initiate these events [13].
  • The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity [28].
  • The region between the DFF45 and KIF1B genes was defined as homozygous deletion by Southern blotting [29].
  • Apoptosis in RCC-91 cells was accompanied by activation of caspases-3 and -9; cleavage of PARP and DFF45 proteins; typical apoptotic nuclei fragmentation and mitochondrial collapse [30].

Analytical, diagnostic and therapeutic context of DFFA

  • Moreover, by real-time RT-PCR expression study, we found the mRNA level of DFFA to be significantly (p=0.038) reduced by a factor of 1.7 times in NB tumors of unfavorable outcome [31].
  • We have also performed studies of the DFFA expression in tumors using real-time PCR [31].
  • Expression, purification, crystallization of fragments from the C-terminal region of DFF45/ICAD [3].
  • Allelism tests indicated that resistance genes in SW8 and SW34 may be allelic to H26 and H13 or correspond to paralogs at both loci, respectively [32].
  • We reviewed the clinical and radiological findings of 93 consecutive patients with 111 extracranial internal carotid (ICAD) and vertebral artery (VAD) dissections and one concomitant intracranial VAD; 83% of the patients had unilateral and 17% multiple vessel dissections [33].


  1. Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours. Abel, F., Sjöberg, R.M., Ejeskär, K., Krona, C., Martinsson, T. Br. J. Cancer (2002) [Pubmed]
  2. Expression of ICAD-l and ICAD-S in human brain tumor and its cleavage upon activation of apoptosis by anti-Fas antibody. Masuoka, J., Shiraishi, T., Ichinose, M., Mineta, T., Tabuchi, K. Jpn. J. Cancer Res. (2001) [Pubmed]
  3. Expression, purification, crystallization of fragments from the C-terminal region of DFF45/ICAD. Ding, H., Qiu, S., Li, S., Symersky, J., Green, T.J., Luo, M. Acta Crystallogr. D Biol. Crystallogr. (2003) [Pubmed]
  4. Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma. Konishi, S., Ishiguro, H., Shibata, Y., Kudo, J., Terashita, Y., Sugiura, H., Koyama, H., Kimura, M., Sato, A., Shinoda, N., Kuwabara, Y., Fujii, Y. Cancer (2002) [Pubmed]
  5. 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. Lugovskoy, A.A., Zhou, P., Chou, J.J., McCarty, J.S., Li, P., Wagner, G. Cell (1999) [Pubmed]
  6. Activation of the innate immunity in Drosophila by endogenous chromosomal DNA that escaped apoptotic degradation. Mukae, N., Yokoyama, H., Yokokura, T., Sakoyama, Y., Nagata, S. Genes Dev. (2002) [Pubmed]
  7. Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells. Alam, A., Cohen, L.Y., Aouad, S., Sékaly, R.P. J. Exp. Med. (1999) [Pubmed]
  8. Direct cleavage of the human DNA fragmentation factor-45 by granzyme B induces caspase-activated DNase release and DNA fragmentation. Sharif-Askari, E., Alam, A., Rhéaume, E., Beresford, P.J., Scotto, C., Sharma, K., Lee, D., DeWolf, W.E., Nuttall, M.E., Lieberman, J., Sékaly, R.P. EMBO J. (2001) [Pubmed]
  9. Determinants of the nuclear localization of the heterodimeric DNA fragmentation factor (ICAD/CAD). Lechardeur, D., Drzymala, L., Sharma, M., Zylka, D., Kinach, R., Pacia, J., Hicks, C., Usmani, N., Rommens, J.M., Lukacs, G.L. J. Cell Biol. (2000) [Pubmed]
  10. DNA fragmentation factor (DFF45): Expression and prognostic value in serous ovarian cancer. Brustmann, H. Pathol. Res. Pract. (2006) [Pubmed]
  11. Method for efficient transfection of in vitro-transcribed mRNA into SK-N-AS and HEK293 cells: difference in the toxicity of nuclear EGFP compared to cytoplasmic EGFP. Ejeskär, K., Fransson, S., Zaibak, F., Ioannou, P.A. Int. J. Mol. Med. (2006) [Pubmed]
  12. Assignment of the DNA fragmentation factor gene (DFFA) to human chromosome bands 1p36.3-->p36.2 by in situ hybridization. Leek, J.P., Carr, I.M., Bell, S.M., Markham, A.F., Lench, N.J. Cytogenet. Cell Genet. (1997) [Pubmed]
  13. Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. Wolf, B.B., Schuler, M., Echeverri, F., Green, D.R. J. Biol. Chem. (1999) [Pubmed]
  14. Cleavage of DFF-45/ICAD by multiple caspases is essential for its function during apoptosis. Tang, D., Kidd, V.J. J. Biol. Chem. (1998) [Pubmed]
  15. Oligomerization state of the DNA fragmentation factor in normal and apoptotic cells. Lechardeur, D., Dougaparsad, S., Nemes, C., Lukacs, G.L. J. Biol. Chem. (2005) [Pubmed]
  16. Inhibition of apoptosis-associated DNA fragmentation activity in nonapoptotic cells: the role of DNA fragmentation factor-45 (DFF45/ICAD). Sabol, S.L., Li, R., Lee, T.Y., Abdul-Khalek, R. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Apoptotic nuclear morphological change without DNA fragmentation. Sakahira, H., Enari, M., Ohsawa, Y., Uchiyama, Y., Nagata, S. Curr. Biol. (1999) [Pubmed]
  18. Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8 and caspase-3 in human lymphomas. Xerri, L., Palmerini, F., Devilard, E., Defrance, T., Bouabdallah, R., Hassoun, J., Birg, F. J. Pathol. (2000) [Pubmed]
  19. ICAD/DFF regulator of apoptotic nuclease is nuclear. Samejima, K., Earnshaw, W.C. Exp. Cell Res. (1998) [Pubmed]
  20. Activation of apoptotic and inflammatory pathways in dysfunctional donor hearts. Birks, E.J., Yacoub, M.H., Burton, P.S., Owen, V., Pomerance, A., O'Halloran, A., Banner, N.R., Khaghani, A., Latif, N. Transplantation (2000) [Pubmed]
  21. Growth phase-dependent expression of ICAD-L/DFF45 modulates the pattern of apoptosis in human colonic cancer cells. Charrier, L., Jarry, A., Toquet, C., Bou-Hanna, C., Chedorge, M., Denis, M., Vallette, G., Laboisse, C.L. Cancer Res. (2002) [Pubmed]
  22. Merbarone induces activation of caspase-activated DNase and excision of chromosomal DNA loops from the nuclear matrix. Otake, Y., Mims, A., Fernandes, D.J. Mol. Pharmacol. (2006) [Pubmed]
  23. MST1-JNK promotes apoptosis via caspase-dependent and independent pathways. Ura, S., Masuyama, N., Graves, J.D., Gotoh, Y. Genes Cells (2001) [Pubmed]
  24. Antiapoptotic regulation by hepatitis C virus core protein through up-regulation of inhibitor of caspase-activated DNase. Sacco, R., Tsutsumi, T., Suzuki, R., Otsuka, M., Aizaki, H., Sakamoto, S., Matsuda, M., Seki, N., Matsuura, Y., Miyamura, T., Suzuki, T. Virology (2003) [Pubmed]
  25. Identification of the nuclear factor HMG2 as an activator for DFF nuclease activity. Toh, S.Y., Wang, X., Li, P. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  26. The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated DNase to the nuclear phenotype and DNA degradation during apoptosis. Yuste, V.J., Sánchez-López, I., Solé, C., Moubarak, R.S., Bayascas, J.R., Dolcet, X., Encinas, M., Susin, S.A., Comella, J.X. J. Biol. Chem. (2005) [Pubmed]
  27. Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis. Rashmi, R., Kumar, S., Karunagaran, D. Carcinogenesis (2004) [Pubmed]
  28. The CIDEA gene V115F polymorphism is associated with obesity in Swedish subjects. Dahlman, I., Kaaman, M., Jiao, H., Kere, J., Laakso, M., Arner, P. Diabetes (2005) [Pubmed]
  29. Homozygous deletion in a neuroblastoma cell line defined by a high-density STS map spanning human chromosome band 1p36. Chen, Y.Z., Soeda, E., Yang, H.W., Takita, J., Chai, L., Horii, A., Inazawa, J., Ohki, M., Hayashi, Y. Genes Chromosomes Cancer (2001) [Pubmed]
  30. Renal carcinoma cells undergo apoptosis without oligonucleosomal DNA fragmentation. Yamaguchi, K., Uzzo, R., Dulin, N., Finke, J.H., Kolenko, V. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  31. Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors. Abel, F., Sjöberg, R.M., Krona, C., Nilsson, S., Martinsson, T. Int. J. Oncol. (2004) [Pubmed]
  32. Genetic characterization and molecular mapping of Hessian fly resistance genes derived from Aegilops tauschii in synthetic wheat. Wang, T., Xu, S.S., Harris, M.O., Hu, J., Liu, L., Cai, X. Theor. Appl. Genet. (2006) [Pubmed]
  33. Extracranial internal carotid and vertebral artery dissections: angiographic spectrum, course and prognosis. Pelkonen, O., Tikkakoski, T., Leinonen, S., Pyhtinen, J., Lepojärvi, M., Sotaniemi, K. Neuroradiology. (2003) [Pubmed]
WikiGenes - Universities