title: FANCD2 is a target for caspase 3 during DNA damage-induced apoptosis.
abstract: The Fanconi anemia (FA) pathway, of which the FANCD2 protein is a key component, plays crucial roles in the maintenance of hematopoietic stem cells and suppression of carcinogenesis. However, the function of FANCD2 remains unclear. Here, we report that FANCD2 is a novel and specific substrate of caspase 3. Cleavage of FANCD2 by caspase 3 did not require either the FA core complex or mono-ubiquitylation of FANCD2, and was stimulated by p53. In addition, we identified the cleavage sites and generated cell lines that stably express a caspase-resistant FANCD2 mutant. Our data suggest that FANCD2 is regulated by caspase-mediated degradation during apoptosis induced by DNA damage.
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe, Hyogo 657-8501, Japan; Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe, Hyogo 657-8501, Japan. Electronic address: wsakai@phoenix.kobe-u.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakai
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe, Hyogo 657-8501, Japan; Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe, Hyogo 657-8501, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
mesh_terms: D017209:Apoptosis; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D004249:DNA Damage; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3
keywords: Apoptosis; Caspase; DNA repair; FANCD2; Fanconi anemia