Executioner caspase-3 and caspase-7 are functionally distinct proteases.

Proceedings of the National Academy of Sciences of the United States of America
John G WalshSeamus J Martin

Abstract

Members of the caspase family of cysteine proteases play central roles in coordinating the stereotypical events that occur during apoptosis. Because the major executioner caspases, caspase-3 and caspase-7, exhibit almost indistinguishable activity toward certain synthetic peptide substrates, this has led to the widespread view that these proteases occupy functionally redundant roles within the cell death machinery. However, the distinct phenotypes of mice deficient in either of these caspases, as well as mice deficient in both, is at odds with this view. These distinct phenotypes could be related to differences in the relative expression levels of caspase-3 and caspase-7 in vivo, or due to more fundamental differences between these proteases in terms of their ability to cleave natural substrates. Here we show that caspase-3 and caspase-7 exhibit differential activity toward multiple substrate proteins, including Bid, XIAP, gelsolin, caspase-6, and cochaperone p23. Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. Our observations provide a molecular basis for the different phenotypes seen in mice lacking either caspase an...Continue Reading

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Citations

Apr 18, 2009·Apoptosis : an International Journal on Programmed Cell Death·Yael Feinstein-Rotkopf, Eli Arama
Jul 20, 2010·Apoptosis : an International Journal on Programmed Cell Death·Juan A MartinezStephen F Larner
Jun 17, 2010·Molecular Neurobiology·Andrew H Wyllie
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Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yufei YuRenato Rozental
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dave BoucherJean-Bernard Denault
May 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nathan D ThomsenJames A Wells
Jul 21, 2009·The Journal of Biological Chemistry·Juliette GafniLisa M Ellerby
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Jul 16, 2011·The Journal of Biological Chemistry·John G WalshSeamus J Martin
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