par Lamkanfi, Mohamed;D'Hondt, Kathleen;Vande Walle, Lieselotte;Van Gurp, Marjan;Denecker, Geertrui;Demeulemeester, Jill;Kalai, Michaël ;Declercq, Wim;Saelens, Xavier;Vandenabeele, Peter
Référence The Journal of biological chemistry, 280, 8, page (6923-6932)
Publication Publié, 2005-02
Référence The Journal of biological chemistry, 280, 8, page (6923-6932)
Publication Publié, 2005-02
Article révisé par les pairs
Résumé : | 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-κB 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-κB 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-κB and p38 MAPK. These results demonstrate the inducible assembly of a novel protein complex consisting of caspase-2, TRAF2, and RIP1 that activates NF-κB and p38 MAPK through the caspase recruitment domain of caspase-2 independently of its proteolytic activity. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc. |