Specific Cleavage of α-Fodrin during Fas- and Tumor Necrosis Factor-induced Apoptosis Is Mediated by an Interleukin-1β-converting Enzyme/Ced-3 Protease Distinct from the Poly(ADP-ribose) Polymerase Protease
Author
Cryns, Vincent L.
Bergeron, Louise
Zhu, Hong
Li, Honglin
Yuan, Junying
Published Version
https://doi.org/10.1074/jbc.271.49.31277Metadata
Show full item recordCitation
Cryns, Vincent L., Louise Bergeron, Hong Zhu, Honglin Li, and Junying Yuan. 1996. “Specific Cleavage of α-Fodrin during Fas- and Tumor Necrosis Factor-Induced Apoptosis Is Mediated by an Interleukin-1β-Converting Enzyme/Ced-3 Protease Distinct from the Poly(ADP-Ribose) Polymerase Protease.” Journal of Biological Chemistry 271 (49): 31277–82. https://doi.org/10.1074/jbc.271.49.31277.Abstract
Interleukin 1 beta-converting enzyme (ICE)/Ced-3 proteases play a critical role in apoptosis. One well characterized substrate of these proteases is the DNA repair enzyme poly(ADP-ribose) polymerase. We report here that alpha-fodrin, an abundant membrane-associated cytoskeletal protein, is cleaved rapidly and specifically during Fas- and tumor necrosis factor-induced apopto sis; this cleavage is mediated by an ICE/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. Studies in cells treated with these apoptotic stimuli reveal that both fodrin and poly(ADP-ribose) polymerase proteolysis are inhibited by acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and CrmA, specific inhibitors of ICE/Ced-3 proteases. However, fodrin proteolysis can be distinguished from poly(ADP-ribose) polymerase prote olysis by its relative insensitivity to acetyl-Asp-Glu-Val-Asp aldehyde (DEVD-CHO), a selective inhibitor of a subset of ICE/Ced-3 proteases that includes CPP32. DEVD-CHO protects cells from Fas induced apoptosis but does not prevent fodrin proteolysis, indicating that cleavage of this protein can be uncoupled from apoptotic cell, death. Moreover, purified fodrin is cleaved in vitro by CPP32 (but not by ICE) into fragments of the same size observed in vivo during apoptosis. These findings suggest that fodrin proteolysis in vivo may reflect the activity of multiple ICE/Ced-3 proteases whose partial sensitivity to DEVD-CHO reflects a limited contribution from CPP32, or an ICE/Ced-3 protease less sensitive than CPP32 to DEVD-CHO inhibition.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483483
Collections
- HMS Scholarly Articles [17843]
Contact administrator regarding this item (to report mistakes or request changes)