Tumor necrosis factor-mediated cell death: to break or to burst,that’s the question |
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Authors: | Franky Van Herreweghe Nele Festjens Wim Declercq Peter Vandenabeele |
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Institution: | (1) Unit For Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, VIB, Technologiepark 927, 9052 Ghent (Zwijnaarde), Belgium;(2) Unit for Molecular Signalling and Cell Death, Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium;(3) Unit for Molecular Glycobiology, Department for Molecular Biomedical Research, VIB, Ghent University, Technologiepark 927, 9052 Ghent, Belgium;(4) Laboratory for Protein Biochemistry and Biomolecular Engineering, Department of Biochemistry and Microbiology, Ghent University, Ledeganckstraat 35, 9052 Ghent, Belgium; |
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Abstract: | In this review, we discuss the signal-transduction pathways of three major cellular responses induced by tumor necrosis factor
(TNF): cell survival through NF-κB activation, apoptosis, and necrosis. Recruitment and activation of caspases plays a crucial
role in the initiation and execution of TNF-induced apoptosis. However, experimental inhibition of caspases reveals an alternative
cell death pathway, namely necrosis, also called necroptosis, suggesting that caspases actively suppress the latter outcome.
TNF-induced necrotic cell death crucially depends on the kinase activity of receptor interacting protein serine-threonine
kinase 1 (RIP1) and RIP3. It was recently demonstrated that ubiquitination of RIP1 determines whether it will function as
a pro-survival or pro-cell death molecule. Deeper insight into the mechanisms that control the molecular switches between
cell survival and cell death will help us to understand why TNF can exert so many different biological functions in the etiology
and pathogenesis of human diseases. |
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