The CED-3/ICE-like Protease Mch2 Is Activated during Apoptosis and Cleaves the Death Substrate Lamin A*
- From the Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109 and the
- ‡ Department of Medicine, Evanston Hospital and Northwestern University Medical School, Evanston, Illinois 60201
- § To whom correspondence should be addressed: Dept. of Pathology, University of Michigan Medical School, 1301 Catherine St., Box 0602, Ann Arbor, MI 48109. Fax: 313-764-4308; E-mail: vmdixit{at}umich.edu
Abstract
Phylogenetic analysis of the CED-3/ICE family of cysteine proteases suggests the existence of a subfamily most related to the Caenorhabditis elegans death gene ced-3 and includes Yama (CPP32, apopain), LAP3 (Mch3, CMH1), and Mch2. Here, we show that Mch2 is processed from its zymogen form to a proteolytically active dimeric species during execution of the apoptotic program and by the cytotoxic T cell death protease granzyme B. Additionally, like Yama and LAP3, Mch2 functions downstream of the death inhibitors Bcl-2, Bcl-xL, and CrmA. Importantly, Mch2, but not Yama or LAP3, is capable of cleaving lamin A to its signature apoptotic fragment, indicating that Mch2 is an apoptotic laminase.
Footnotes
-
↵* This work was supported by National Institutes of Health Grants CA64803 and CA68769. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- IL-1β
-
interleukin-1β
- PARP
-
poly(ADP-ribose) polymerase
- TLCK
-
Tos-Lys-CH2Cl
- ICE
-
interleukin-1β converting enzyme
- PAGE
-
polyacrylamide gel electrophoresis.
-
- Received May 6, 1996.
- Revision received May 22, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
