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http://purl.uniprot.org/citations/17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17470554http://www.w3.org/2000/01/rdf-schema#comment"Alkylating DNA damage induces a necrotic type of programmed cell death through the poly(ADP-ribose) polymerases (PARP) and apoptosis-inducing factor (AIF). Following PARP activation, AIF is released from mitochondria and translocates to the nucleus, where it causes chromatin condensation and DNA fragmentation. By employing a large panel of gene knockout cells, we identified and describe here two essential molecular links between PARP and AIF: calpains and Bax. Alkylating DNA damage initiated a p53-independent form of death involving PARP-1 but not PARP-2. Once activated, PARP-1 mediated mitochondrial AIF release and necrosis through a mechanism requiring calpains but not cathepsins or caspases. Importantly, single ablation of the proapoptotic Bcl-2 family member Bax, but not Bak, prevented both AIF release and alkylating DNA damage-induced death. Thus, Bax is indispensable for this type of necrosis. Our data also revealed that Bcl-2 regulates N-methyl-N'-nitro-N'-nitrosoguanidine-induced necrosis. Finally, we established the molecular ordering of PARP-1, calpains, Bax, and AIF activation, and we showed that AIF downregulation confers resistance to alkylating DNA damage-induced necrosis. Our data shed new light on the mechanisms regulating AIF-dependent necrosis and support the notion that, like apoptosis, necrosis could be a highly regulated cell death program."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.org/dc/terms/identifier"doi:10.1128/mcb.02141-06"xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Moubarak R.S."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Susin S.A."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Yuste V.J."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Menissier-de Murcia J."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Greer P.A."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Artus C."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/author"Bouharrour A."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/name"Mol Cell Biol"xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/pages"4844-4862"xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/title"Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis."xsd:string
http://purl.uniprot.org/citations/17470554http://purl.uniprot.org/core/volume"27"xsd:string
http://purl.uniprot.org/citations/17470554http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17470554
http://purl.uniprot.org/citations/17470554http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17470554
http://purl.uniprot.org/uniprot/#_A0A0A6YVX0-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_A0A0A6YX03-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_A0A0A6YY63-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_A0A0R4J1C2-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_A0A165ELP6-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_P11103-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_Q07813-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554
http://purl.uniprot.org/uniprot/#_A0A1B0GT35-mappedCitation-17470554http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17470554