Editors' ChoiceApoptosis

Calpain and Caspase Cross Talk

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Science's STKE  29 Aug 2000:
Vol. 2000, Issue 47, pp. tw5
DOI: 10.1126/stke.2000.47.tw5

Caspases are cysteine proteases that regulate apoptosis, and some are activated by proteolytic cleavage of their proenzyme form by other caspases. However, Nakagawa and Yuan report that procaspase-12, localized at the cytoplasmic face of the endoplasmic reticulum (ER), is cleaved and activated by a noncaspase protease called calpain. Activation of caspase-12 in glial cells, in response to ER stress agents, was blocked when cells were treated with a calpain inhibitor. Activation of caspase-12 in these cells generated proteolytic caspase-12 fragments that were also observed in vitro by using purified proteins. The authors propose that activation of calpain by an increase in intracellular calcium, a condition that also promotes calpain translocation from the cytosol to membranes, may promote activation of caspase-12 and may play an important role in mediating neuronal degeneration.

Nakagawa, T., and Yuan, J. (2000) Cross-talk between two cysteine protease families: Activation of caspase-12 by calpain in apoptosis. J. Cell Biol. 150: 887-894. [Abstract] [Full Text]

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