title: The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC.
abstract: Fanconi anemia is an autosomal recessive disorder characterized by aplastic anemia, cancer susceptibility, and cellular sensitivity to mitomycin C. The 6 known Fanconi anemia gene products (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG proteins) interact in a common pathway. The monoubiquitination and nuclear foci formation of FANCD2 are essential for the function of this pathway. FANCA, FANCC, FANCG, and FANCF proteins form a multisubunit nuclear complex (FA complex) required for FANCD2 monoubiquitination. Because FANCE and FANCC interact in vitro and FANCE is required for FANCD2 monoubiquitination, we reasoned that FANCE is a component of the FA complex in vivo. Here we demonstrate that retroviral transduction of Fanconi anemia subtype E (FA-E) cells with the FANCE cDNA restores the nuclear accumulation of FANCC protein, FANCA-FANCC complex formation, monoubiquitination and nuclear foci formation of FANCD2, and mitomycin C resistance. Hemagglutinin (HA)-tagged FANCE protein localizes diffusely in the nucleus. In normal cells, HA-tagged FANCE protein coimmunoprecipitates with FANCA, FANCC, and FANCG but not with FANCD2. Our data indicate that FANCE is a component of the nuclear FA complex in vivo and is required for the monoubiquitination of FANCD2 and the downstream events in the FA pathway.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, and the Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
mesh_terms: D018797:Cell Cycle Proteins; D002458:Cell Fractionation; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000097:blood*; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D052239:Fanconi Anemia Complementation Group E Protein; D051856:Fanconi Anemia Complementation Group Proteins; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; C499905:FANCD2 protein, human; C499907:FANCE protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D052239:Fanconi Anemia Complementation Group E Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins