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http://purl.uniprot.org/citations/22253444http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22253444http://www.w3.org/2000/01/rdf-schema#comment"Apoptotic cell death is characterized by nuclear fragmentation and oligonucleosomal DNA degradation, mediated by the caspase-dependent specific activation of DFF40/CAD endonuclease. Here, we describe how, upon apoptotic stimuli, SK-N-AS human neuroblastoma-derived cells show apoptotic nuclear morphology without displaying concomitant internucleosomal DNA fragmentation. Cytotoxicity afforded after staurosporine treatment is comparable with that obtained in SH-SY5Y cells, which exhibit a complete apoptotic phenotype. SK-N-AS cell death is a caspase-dependent process that can be impaired by the pan-caspase inhibitor q-VD-OPh. The endogenous inhibitor of DFF40/CAD, ICAD, is correctly processed, and dff40/cad cDNA sequence does not reveal mutations altering its amino acid composition. Biochemical approaches show that both SH-SY5Y and SK-N-AS resting cells express comparable levels of DFF40/CAD. However, the endonuclease is poorly expressed in the cytosolic fraction of healthy SK-N-AS cells. Despite this differential subcellular distribution of DFF40/CAD, we find no differences in the subcellular localization of both pro-caspase-3 and ICAD between the analyzed cell lines. After staurosporine treatment, the preferential processing of ICAD in the cytosolic fraction allows the translocation of DFF40/CAD from this fraction to a chromatin-enriched one. Therefore, the low levels of cytosolic DFF40/CAD detected in SK-N-AS cells determine the absence of DNA laddering after staurosporine treatment. In these cells DFF40/CAD cytosolic levels can be restored by the overexpression of their own endonuclease, which is sufficient to make them proficient at degrading their chromatin into oligonucleosome-size fragments after staurosporine treatment. Altogether, the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m111.290718"xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Yuste V.J."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Comella J.X."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Sanchez-Osuna M."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Iglesias-Guimarais V."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Casanelles E."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Gabernet G."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Garcia-Belinchon M."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/author"Gil-Guinon E."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/pages"7766-7779"xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/title"Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease."xsd:string
http://purl.uniprot.org/citations/22253444http://purl.uniprot.org/core/volume"287"xsd:string
http://purl.uniprot.org/citations/22253444http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22253444
http://purl.uniprot.org/citations/22253444http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22253444
http://purl.uniprot.org/uniprot/P55210#attribution-08E0A1B76F609381FCCE250851EB63D0http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22253444
http://purl.uniprot.org/uniprot/P55212#attribution-08E0A1B76F609381FCCE250851EB63D0http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22253444
http://purl.uniprot.org/uniprot/P42574#attribution-08E0A1B76F609381FCCE250851EB63D0http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22253444