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D.H. Dockrell  Clinical Microbiology and Infection 

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1 The multiple roles of Fas ligand in the pathogenesis of infectious diseases 
D.H. Dockrell  Clinical Microbiology and Infection  Volume 9, Issue 8, Pages (August 2003) DOI: /j x Copyright © 2003 European Society of Clinical Infectious Diseases Terms and Conditions

2 Figure 1 (A) Fas-mediated signal transduction. Fas trimers recruit the Fas-associated death domain (FAAD) that couples Fas to procaspase-8 (Fas-linked interleukin-converting enzyme (FLICE)). Fas-interacting serine/threonine kinase/homeodomain-interacting protein kinase (FIST/HIPK3) phosphorylates FAAD to promote binding to Fas. FLIP (FLICE-linked inhibitory protein) binds to FAAD and inhibits procaspase-8 binding. Caspase-8, when activated, can cleave Bid, which results in the release of cytochrome c (cyt c) from the mitochondrion. Cytochrome c forms a complex with procaspase-9 and apoptosis protease-activating factor 1 (Apaf-1). Caspase-8 and 9 activate caspase-3, and apoptosis is induced. Fas also signals via receptor-interacting protein (RIP) and RIP-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD) to induce cell death, and can activate mitogen-activated protein kinase kinase kinase (MAP3K) and c-Jun N-terminal kinases (JNK) via death domain-associated protein (DAXX). In addition, proposed binding of TNF receptor-associated death domain (TRAAD) and TNF receptor-associated factor 2 (TRAF 2) result in NFκB activation after dissociation from its inhibitor IκB. FasL transcription is regulated by a number of promoters, including NFκB and the nuclear factor of activated T-cells (NFAT). FasL is cleaved from the cell membrane by matrix metalloproteinases (MMP). Broken lines denote inhibitors of specific interactions. (B) HIV-1 proteins that modulate apoptosis. The HIV-1 proteins that modulate apoptosis are shown in relation to Fas-mediated signaling. +ve denotes enhancement, and –ve denotes inhibition. Clinical Microbiology and Infection 2003 9, DOI: ( /j x) Copyright © 2003 European Society of Clinical Infectious Diseases Terms and Conditions


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