Journal
MOLECULAR CELL
Volume 31, Issue 3, Pages 415-421Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2008.06.008
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Funding
- NIH [AI057838, CA108872, AI071274]
- Leukemia and Lymphoma Society Scholar Award
- American Gastroenterology Association Funderburg Research Scholar Award
- [T32CA09140]
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Caspase-8, an initiator caspase involved in lymphocyte apoptosis, is paradoxically required for lymphocyte proliferation. It is not understood how caspase-8 is controlled during antigenic signaling to allow for activation while averting the triggering of apoptosis. Here, we show that caspase-8 undergoes limited activation upon antigenic stimulation, and this activation is dependent on the paracaspase MALT1. The paracaspase domain of MALT1, in a protease-independent manner, induces caspase-8 activation through direct association. MALT1 diminishes the activation of apoptotic effector caspases, but it does not alter the activity of caspase-8 toward c-FLIPL, which is required for antigenic signaling. Mutants of MALT1 that fail to activate caspase-8 and permit c-FLIPL cleavage cannot facilitate NF-kappa B activation or IL-2 induction. Our results reveal a mechanism that utilizes a protease potentially deadly to the cell for proliferative signaling and demonstrate a functional connection between the caspase and paracaspase families to enable non-apoptotic processes.
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