A novel caspase-2 complex containing TRAF2 and RIP1 |
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Authors: | Lamkanfi Mohamed D'hondt Kathleen Vande Walle Lieselotte van Gurp Marjan Denecker Geertrui Demeulemeester Jill Kalai Michael Declercq Wim Saelens Xavier Vandenabeele Peter |
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Institution: | Unit of Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, Ghent University and Flemish Interuniversity Institute for Biotechnology, Technologiepark 927, Zwijnaarde B-9052, Belgium. |
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Abstract: | 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. |
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