title: The CED-3/ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A.
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.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: K
authors.initials: K
authors.lastname: Orth
authors.forename: A M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: M
authors.initials: M
authors.lastname: Garg
authors.forename: C J
authors.initials: CJ
authors.lastname: Froelich
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D017209:Apoptosis; D053178:Caspase 6; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D034904:Lamin Type A; D034882:Lamins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D019311:Staurosporine; D013379:Substrate Specificity
chemical_list: D000470:Alkaloids; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins; C505514:CASP6 protein, human; D053178:Caspase 6; D003546:Cysteine Endopeptidases; D019311:Staurosporine