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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2002-6-27
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pubmed:abstractText |
Fanconi anemia (FA) and ataxia telangiectasia (AT) are clinically distinct autosomal recessive disorders characterized by spontaneous chromosome breakage and hematological cancers. FA cells are hypersensitive to mitomycin C (MMC), while AT cells are hypersensitive to ionizing radiation (IR). Here, we identify the Fanconi anemia protein, FANCD2, as a link between the FA and ATM damage response pathways. ATM phosphorylates FANCD2 on serine 222 in vitro. This site is also phosphorylated in vivo in an ATM-dependent manner following IR. Phosphorylation of FANCD2 is required for activation of an S phase checkpoint. The ATM-dependent phosphorylation of FANCD2 on S222 and the FA pathway-dependent monoubiquitination of FANCD2 on K561 are independent posttranslational modifications regulating discrete cellular signaling pathways. Biallelic disruption of FANCD2 results in both MMC and IR hypersensitivity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FANCD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fanconi Anemia Complementation...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
109
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
459-72
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:12086603-Ataxia Telangiectasia,
pubmed-meshheading:12086603-Cell Cycle Proteins,
pubmed-meshheading:12086603-Cell Line, Transformed,
pubmed-meshheading:12086603-Cell Nucleus,
pubmed-meshheading:12086603-DNA-Binding Proteins,
pubmed-meshheading:12086603-Fanconi Anemia,
pubmed-meshheading:12086603-Fanconi Anemia Complementation Group D2 Protein,
pubmed-meshheading:12086603-G1 Phase,
pubmed-meshheading:12086603-G2 Phase,
pubmed-meshheading:12086603-Genes, cdc,
pubmed-meshheading:12086603-HeLa Cells,
pubmed-meshheading:12086603-Humans,
pubmed-meshheading:12086603-Mitomycin,
pubmed-meshheading:12086603-Mutation,
pubmed-meshheading:12086603-Nuclear Proteins,
pubmed-meshheading:12086603-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:12086603-Phosphorylation,
pubmed-meshheading:12086603-Phosphoserine,
pubmed-meshheading:12086603-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12086603-Radiation, Ionizing,
pubmed-meshheading:12086603-S Phase,
pubmed-meshheading:12086603-Signal Transduction,
pubmed-meshheading:12086603-Tumor Suppressor Proteins,
pubmed-meshheading:12086603-Ubiquitin
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pubmed:year |
2002
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pubmed:articleTitle |
Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways.
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pubmed:affiliation |
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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