Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10904563 | Experimental Cell Research | 2011 | 12 Pages |
Abstract
We report here the cleavage of the c-Jun N-terminal Kinase (JNK) pathway scaffold protein, JNK Interacting Protein-1 (JIP1), by caspases during both Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and staurosporine-induced apoptosis in HeLa cells. During the initiation of apoptosis, maximal JNK activation is observed when JIP1 is intact, whereas cleavage of JIP1 correlates with JNK inactivation and progression of apoptosis. JIP1 is cleaved by caspase-3 at two sites, leading to disassembly of the JIP1/JNK complex. Inhibition of JIP1 cleavage by the caspase-3 inhibitor DEVD.fmk inhibits this disassembly, and is accompanied by sustained JNK activation. These data suggest that TRAIL and staurosporine induce JNK activation in a caspase-3-independent manner and that caspase-3-mediated JIP1 cleavage plays a role in JNK inactivation via scaffold disassembly during the execution phase of apoptosis. Caspase-mediated cleavage of JIP scaffold proteins may therefore represent an important mechanism for modulation of JNK signalling during apoptotic cell death.
Keywords
NF-κBTNF Receptor Associated Death Domainreceptor interacting protein kinaseIB1MAPKK kinasezVAD.fmkTNFJIPMAPKKKMAPKKc-jun amino-terminal kinaseTRADDTRAFPARPFADDPBSJnkDTTGTPase Activating ProteinMAPKMAPK kinaseEDTAethylene diamine tetra-acetic acidFas-associated death domainApoptosisdithiothreitolGAPPOSHtumour necrosis factorTNF receptor associated factornuclear factor κBPhosphate buffered salineTRAILTNF-related apoptosis inducing ligandRIPmitogen-activated protein kinaseCaspase-3Hela
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Authors
Mahesh Vaishnav, Marion MacFarlane, Martin Dickens,