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Gene Review

Dffa  -  DNA fragmentation factor, alpha subunit

Mus musculus

Synonyms: A330085O09Rik, DFF-45, DFF35, DNA fragmentation factor 45 kDa subunit, DNA fragmentation factor subunit alpha, ...
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Disease relevance of Dffa


High impact information on Dffa


Biological context of Dffa


Anatomical context of Dffa

  • CAD was predominantly associated with ICAD-L in these cell lines [13].
  • In contrast, reticulocyte lysates stimulated ICAD-L- and ATP-dependent renaturation of denatured CAD without requiring a high concentration of reducing agents [14].
  • Among eight different caspases examined, recombinant caspases 3 and 7 specifically cleaved ICAD synthesized in a cell-free system [10].
  • We also show expression of a caspase cleavage-resistant form of ICAD (ICAD-DM) in Jurkat and HeLa cells abolished DNA fragmentation and also dramatically reduced histone release in apoptotic cells [15].
  • We showed that CAD and ICAD are co-localized in microsome, nuclei and cytosol in unstimulated thymocytes [16].

Associations of Dffa with chemical compounds


Physical interactions of Dffa

  • In proliferating cells, CAD is complexed with ICAD (inhibitor of CAD) and its DNase activity is suppressed [12].

Enzymatic interactions of Dffa


Regulatory relationships of Dffa

  • Following in vivo TCR engagement, ICAD located in cytosol and microsome was degraded and the resulting activated CAD induced chromosomal DNA fragmentation [16].
  • (+)-Catechin partially inhibited the activation of caspase-3, thereby both cleavage of poly (ADP-ribose) polymerase (PARP) and degradation of inhibitor of caspase-activated DNase (ICAD) were effectively abolished [22].
  • Cytosolic nuclease activated by caspase-3 and inhibited by DFF-45 [23].

Other interactions of Dffa


Analytical, diagnostic and therapeutic context of Dffa


  1. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., Nagata, S. Nature (1998) [Pubmed]
  2. Presence of DNA fragmentation and lack of neuroprotective effect in DFF45 knockout mice subjected to traumatic brain injury. Yakovlev, A.G., Di, X., Movsesyan, V., Mullins, P.G., Wang, G., Boulares, H., Zhang, J., Xu, M., Faden, A.I. Mol. Med. (2001) [Pubmed]
  3. Dna fragmentation factor 45 mutant mice exhibit resistance to kainic acid-induced neuronal cell death. Zhang, J., Lee, H., Agarwala, A., Wen Lou, D., Xu, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  4. Mechanism of acetaminophen-induced apoptosis in cultured cells: roles of caspase-3, DNA fragmentation factor, and the Ca2+ and Mg2+ endonuclease DNAS1L3. Boulares, A.H., Ren, T. Basic & clinical pharmacology & toxicology. (2004) [Pubmed]
  5. Cidea-deficient mice have lean phenotype and are resistant to obesity. Zhou, Z., Yon Toh, S., Chen, Z., Guo, K., Ng, C.P., Ponniah, S., Lin, S.C., Hong, W., Li, P. Nat. Genet. (2003) [Pubmed]
  6. Endonuclease G is an apoptotic DNase when released from mitochondria. Li, L.Y., Luo, X., Wang, X. Nature (2001) [Pubmed]
  7. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Sakahira, H., Enari, M., Nagata, S. Nature (1998) [Pubmed]
  8. Loss of splicing factor ASF/SF2 induces G2 cell cycle arrest and apoptosis, but inhibits internucleosomal DNA fragmentation. Li, X., Wang, J., Manley, J.L. Genes Dev. (2005) [Pubmed]
  9. Structure and promoter analysis of murine CAD and ICAD genes. Kawane, K., Fukuyama, H., Adachi, M., Sakahira, H., Copeland, N.G., Gilbert, D.J., Jenkin, N.A., Nagata, S. Cell Death Differ. (1999) [Pubmed]
  10. Involvement of caspase 3-activated DNase in internucleosomal DNA cleavage induced by diverse apoptotic stimuli. McIlroy, D., Sakahira, H., Talanian, R.V., Nagata, S. Oncogene (1999) [Pubmed]
  11. Structure of the CAD domain of caspase-activated DNase and interaction with the CAD domain of its inhibitor. Uegaki, K., Otomo, T., Sakahira, H., Shimizu, M., Yumoto, N., Kyogoku, Y., Nagata, S., Yamazaki, T. J. Mol. Biol. (2000) [Pubmed]
  12. Enzymatic active site of caspase-activated DNase (CAD) and its inhibition by inhibitor of CAD. Sakahira, H., Takemura, Y., Nagata, S. Arch. Biochem. Biophys. (2001) [Pubmed]
  13. Functional differences of two forms of the inhibitor of caspase-activated DNase, ICAD-L, and ICAD-S. Sakahira, H., Enari, M., Nagata, S. J. Biol. Chem. (1999) [Pubmed]
  14. Specific chaperone-like activity of inhibitor of caspase-activated DNase for caspase-activated DNase. Sakahira, H., Iwamatsu, A., Nagata, S. J. Biol. Chem. (2000) [Pubmed]
  15. Apoptotic release of histones from nucleosomes. Wu, D., Ingram, A., Lahti, J.H., Mazza, B., Grenet, J., Kapoor, A., Liu, L., Kidd, V.J., Tang, D. J. Biol. Chem. (2002) [Pubmed]
  16. The regulation of DNAse activities in subcellular compartments of activated thymocytes. Nagata, T., Kishi, H., Liu, Q.L., Matsuda, T., Imanaka, T., Tsukada, K., Kang, D., Muraguchi, A. Immunology (2002) [Pubmed]
  17. DNA fragmentation factor 45-deficient cells are more resistant to apoptosis and exhibit different dying morphology than wild-type control cells. Zhang, J., Wang, X., Bove, K.E., Xu, M. J. Biol. Chem. (1999) [Pubmed]
  18. Roles of DNA fragmentation factor and poly(ADP-ribose) polymerase in an amplification phase of tumor necrosis factor-induced apoptosis. Boulares, A.H., Zoltoski, A.J., Yakovlev, A., Xu, M., Smulson, M.E. J. Biol. Chem. (2001) [Pubmed]
  19. Effects of phosphocreatine on apoptosis in a cell-free system. Zhao, Y., Lu, Z., Wu, M., Han, Q., Tao, W., Zhai, Z. J. Biol. Chem. (2001) [Pubmed]
  20. Over expression of inhibitor of caspase 3 activated deoxyribonuclease in human renal cell carcinoma cells enhances their resistance to cytotoxic chemotherapy in vivo. Hara, S., Miyake, H., Arakawa, S., Kamidono, S., Hara, I. J. Urol. (2001) [Pubmed]
  21. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. Inohara, N., Koseki, T., Chen, S., Wu, X., Núñez, G. EMBO J. (1998) [Pubmed]
  22. Elevated levels of DNA repair enzymes and antioxidative enzymes by (+)-catechin in murine microglia cells after oxidative stress. Huang, Q., Wu, L.J., Tashiro, S., Onodera, S., Ikejima, T. Journal of Asian natural products research. (2006) [Pubmed]
  23. Cytosolic nuclease activated by caspase-3 and inhibited by DFF-45. Mitamura, S., Ikawa, H., Mizuno, N., Kaziro, Y., Itoh, H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  24. DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis. Thomas, D.A., Du, C., Xu, M., Wang, X., Ley, T.J. Immunity (2000) [Pubmed]
  25. Caspase activation during apoptotic cell death induced by expanded polyglutamine in N2a cells. Wang, G.H., Mitsui, K., Kotliarova, S., Yamashita, A., Nagao, Y., Tokuhiro, S., Iwatsubo, T., Kanazawa, I., Nukina, N. Neuroreport (1999) [Pubmed]
  26. Large complex formation of the inhibitor of caspase-activated DNase. Kanouchi, H., Nishizaki, H., Minatogawa, Y., Toné, S. Apoptosis (2005) [Pubmed]
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