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http://purl.uniprot.org/citations/11520787http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11520787http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11520787http://www.w3.org/2000/01/rdf-schema#comment"The Fanconi anemia (FA) group C gene product (FANCC) functions to protect cells from cytotoxic and genotoxic effects of cross-linking agents. FANCC is also required for optimal activation of STAT1 in response to cytokine and growth factors and for suppressing cytokine-induced apoptosis by modulating the activity of double-stranded RNA-dependent protein kinase. Because not all FANCC mutations affect STAT1 activation, the hypothesis was considered that cross-linker resistance function of FANCC depends on structural elements that differ from those required for the cytokine signaling functions of FANCC. Structure-function studies were designed to test this notion. Six separate alanine-substituted mutations were generated in 3 highly conserved motifs of FANCC. All mutants complemented mitomycin C (MMC) hypersensitive phenotype of FA-C cells and corrected aberrant posttranslational activation of FANCD2 in FA-C mutant cells. However, 2 of the mutants, S249A and E251A, failed to correct defective STAT1 activation. FA-C lymphoblasts carrying these 2 mutants demonstrated a defect in recruitment of STAT1 to the interferon gamma (IFN-gamma) receptor and GST-fusion proteins bearing S249A and E251A mutations were less efficient binding partners for STAT1 in stimulated lymphoblasts. These same mutations failed to complement the characteristic hypersensitive apoptotic responses of FA-C cells to tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Cells bearing a naturally occurring FANCC mutation (322delG) that preserves this conserved region showed normal STAT1 activation but remained hypersensitive to MMC. The conclusion is that a central highly conserved domain of FANCC is required for functional interaction with STAT1 and that structural elements required for STAT1-related functions differ from those required for genotoxic responses to cross-linking agents. Preservation of signaling capacity of cells bearing the del322G mutation may account for the reduced severity and later onset of bone marrow failure associated with this mutation."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.org/dc/terms/identifier"doi:10.1182/blood.v98.5.1392"xsd:string
http://purl.uniprot.org/citations/11520787http://purl.org/dc/terms/identifier"doi:10.1182/blood.v98.5.1392"xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Diaz J."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Diaz J."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Olson S."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Olson S."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Pang Q."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Pang Q."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Bagby G.C."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Bagby G.C."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Christianson T.A."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Christianson T.A."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Faulkner G.R."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Faulkner G.R."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Keeble W."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Keeble W."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Reifsteck C."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/author"Reifsteck C."xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/name"Blood"xsd:string
http://purl.uniprot.org/citations/11520787http://purl.uniprot.org/core/name"Blood"xsd:string
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