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.
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Authors | Toshiyasu Taniguchi, Alan D D'Andrea |
Journal | Blood
(Blood)
Vol. 100
Issue 7
Pg. 2457-62
(Oct 01 2002)
ISSN: 0006-4971 [Print] United States |
PMID | 12239156
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cell Cycle Proteins
- DNA-Binding Proteins
- FANCC protein, human
- FANCD2 protein, human
- FANCE protein, human
- Fanconi Anemia Complementation Group C Protein
- Fanconi Anemia Complementation Group D2 Protein
- Fanconi Anemia Complementation Group E Protein
- Fanconi Anemia Complementation Group Proteins
- Nuclear Proteins
- Proteins
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Topics |
- Cell Cycle Proteins
- Cell Fractionation
- Cell Line, Transformed
- Cell Nucleus
(metabolism, ultrastructure)
- DNA-Binding Proteins
- Fanconi Anemia
(blood)
- Fanconi Anemia Complementation Group C Protein
- Fanconi Anemia Complementation Group D2 Protein
- Fanconi Anemia Complementation Group E Protein
- Fanconi Anemia Complementation Group Proteins
- Herpesvirus 4, Human
(genetics)
- Humans
- Nuclear Proteins
(metabolism)
- Proteins
(metabolism)
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