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http://purl.uniprot.org/citations/12595532http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12595532http://www.w3.org/2000/01/rdf-schema#comment"Chronic hepatitis C virus (HCV) infection frequently leads to liver cancer. To determine the viral factor(s) potentially involved in viral persistence, we focused our work on NS2, a viral protein of unknown function. To assign a role for NS2, we searched for cellular proteins that interact with NS2. Performing a two-hybrid screen on a human liver cDNA library, we found that NS2 interacted with the liver-specific pro-apoptotic CIDE-B protein. Binding specificity of NS2 for CIDE-B was confirmed by cell-free assays associated with colocalization studies and coprecipitation experiments on human endogenous CIDE-B. CIDE-B, a member of the novel CIDE family of apoptosis-inducing factors, has been reported to show strong cell death-inducing activity in its C-terminal domain. We show that this CIDE-B killing domain is involved in the NS2 interaction. NS2 binding was sufficient to inhibit CIDE-B-induced apoptosis because an NS2 deletion mutant unable to interact with CIDE-B in vitro lost its capacity to interfere with CIDE-B cell death activity. Although it has been reported that CIDE-B-induced apoptosis is characterized by mitochondrial localization, the precise apoptotic mechanism remained unknown. Here, we show that CIDE-B induced cell death in a caspase-dependent manner through cytochrome c release from mitochondria. Furthermore, we found that NS2 counteracted the cytochrome c release induced by CIDE-B. In vivo, the CIDE-B protein level was extremely low in adenovirus-infected transgenic mice expressing the HCV polyprotein compared with that in wild-type mice. We suggest that NS2 interferes with the CIDE-B-induced death pathway and participates in HCV strategies to subvert host cell defense."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m209732200"xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Gripon P."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Guguen-Guillouzo C."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Le Seyec J."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Franck N."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Lerat H."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Hibner U."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Gilot D."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Cannie I."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/author"Erdtmann L."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/pages"18256-18264"xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/title"The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis."xsd:string
http://purl.uniprot.org/citations/12595532http://purl.uniprot.org/core/volume"278"xsd:string
http://purl.uniprot.org/citations/12595532http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12595532
http://purl.uniprot.org/citations/12595532http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12595532
http://purl.uniprot.org/uniprot/Q9UHD4#attribution-71EAE5B584DDD0E84D25E59AE4F1114Bhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/12595532
http://purl.uniprot.org/uniprot/Q9UHD4#attribution-EC2C3BE3F777FD9A20A14D0440AFFF73http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/12595532
http://purl.uniprot.org/uniprot/#_Q9UHD4-mappedCitation-12595532http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12595532
http://purl.uniprot.org/uniprot/Q9UHD4http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/12595532