Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions.
Kang, SJ; Wang, S; Hara, H; Peterson, EP; Namura, S; Amin-Hanjani, S; Huang, Z; Srinivasan, A; Tomaselli, KJ; Thornberry, NA; Moskowitz, MA; Yuan, J
The Journal of cell biology
149
613-22
1999
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Caspase-11, a member of the murine caspase family, has been shown to be an upstream activator of caspase-1 in regulating cytokine maturation. We demonstrate here that in addition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion (MCAO), a mouse model of stroke. Recombinant procaspase-11 can autoprocess itself in vitro. Purified active recombinant caspase-11 cleaves and activates procaspase-3 very efficiently. Using a positional scanning combinatorial library method, we found that the optimal cleavage site of caspase-11 was (I/L/V/P)EHD, similar to that of upstream caspases such as caspase-8 and -9. Our results suggest that caspase-11 is a critical initiator caspase responsible for the activation of caspase-3, as well as caspase-1 under certain pathological conditions. | 10791975
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