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http://purl.uniprot.org/citations/10224289http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10224289http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10224289http://www.w3.org/2000/01/rdf-schema#comment"During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.org/dc/terms/identifier"doi:10.1084/jem.189.9.1489"xsd:string
http://purl.uniprot.org/citations/10224289http://purl.org/dc/terms/identifier"doi:10.1084/jem.189.9.1489"xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"McMichael A.J."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"McMichael A.J."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Wolf D."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Wolf D."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Kraft M."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Kraft M."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Baur A.S."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Baur A.S."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Kolanus W."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Kolanus W."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Laffert B."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Laffert B."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Mongkolsapay J."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Mongkolsapay J."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Screaton G.R."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Screaton G.R."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Xu X.-N."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/author"Xu X.-N."xsd:string
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10224289http://purl.uniprot.org/core/date"1999"xsd:gYear