A Novel Caspase-2 Complex Containing TRAF2 and RIP1
Copyright policy )A Novel Caspase-2 Complex Containing TRAF2 and RIP1
The enzymatic activity of caspases is implicated in the execution of apoptosis and inflammation. Here we demonstrate a novel nonenzymatic function for caspase-2 other than its reported proteolytic role in apoptosis. Caspase-2, unlike caspase-3, -6, -7, -9, -11, -12, and -14, is a potent inducer of NF-kappaB and p38 MAPK activation in a TRAF2-mediated way. Caspase-2 interacts with TRAF1, TRAF2, and RIP1. Furthermore, we demonstrate that endogenous caspase-2 is recruited into a large and inducible protein complex, together with TRAF2 and RIP1. Structure-function analysis shows that NF-kappaB activation occurs independent of enzymatic activity of the protease and that the caspase recruitment domain of caspase-2 is sufficient for the activation of NF-kappaB and p38 MAPK. These results demonstrate the inducible assembly of a novel protein complex consisting of caspase-2, TRAF2, and RIP1 that activates NF-kappaB and p38 MAPK through the caspase recruitment domain of caspase-2 independently of its proteolytic activity.
- Ghent University Belgium
- Université Libre de Bruxelles Belgium
Protein Structure, Biochimie, GTPase-Activating Proteins -- metabolism, Transfection, p38 Mitogen-Activated Protein Kinases, Cell Line, Mice, NF-kappa B -- metabolism, Site-Directed, Animals, Humans, TNF Receptor-Associated Factor 2 -- metabolism, TNF Receptor-Associated Factor 1 -- metabolism, Caspases -- genetics -- metabolism -- physiology, GTPase-Activating Proteins, Caspase 2, NF-kappa B, Biologie moléculaire, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 1, Protein Structure, Tertiary, p38 Mitogen-Activated Protein Kinases -- genetics -- metabolism, Mutagenesis, Caspases, Multiprotein Complexes, Mutagenesis, Site-Directed, Biologie cellulaire, Tertiary
Protein Structure, Biochimie, GTPase-Activating Proteins -- metabolism, Transfection, p38 Mitogen-Activated Protein Kinases, Cell Line, Mice, NF-kappa B -- metabolism, Site-Directed, Animals, Humans, TNF Receptor-Associated Factor 2 -- metabolism, TNF Receptor-Associated Factor 1 -- metabolism, Caspases -- genetics -- metabolism -- physiology, GTPase-Activating Proteins, Caspase 2, NF-kappa B, Biologie moléculaire, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 1, Protein Structure, Tertiary, p38 Mitogen-Activated Protein Kinases -- genetics -- metabolism, Mutagenesis, Caspases, Multiprotein Complexes, Mutagenesis, Site-Directed, Biologie cellulaire, Tertiary
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