Conversion of procaspase-3 to an autoactivating caspase by fusion to the caspase-2 predomain

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dc.contributor.authorColussi, P.
dc.contributor.authorHarvey, N.
dc.contributor.authorShearwin-Whyatt, L.
dc.contributor.authorKumar, S.
dc.date.issued1998
dc.description.abstractCaspases are cysteine proteases that play an essential role in apoptosis. Initial activation of caspases defines the key step in apoptotic execution. Based on primary structure, caspases can be divided into two groups, those with long amino-terminal prodomains (class I), and those with relatively short prodomains (class II). On overexpression in mammalian cells, class I caspases can induce cell death that is dependent on their autocatalytic activity. Recent studies suggest that the long prodomains in some class I caspases are able to mediate dimerization of procaspase molecules, thereby promoting autoprocessing. In this communication, we demonstrate that fusion of the prodomain of a class I caspase (Nedd2/caspase-2) with procaspase-3 greatly augments autocatalysis and apoptosis induction by the chimeric caspase-3 molecule. The chimeric caspase-3 molecules were able to form homodimers in Saccharomyces cerevisiae and were efficiently processed in transfected mammalian cells. These results provide direct evidence for a role of a class I caspase prodomain in caspase autoactivation and processing and establish a basis for functional hierarchy among the two classes of caspases.
dc.description.statementofresponsibilityPaul A. Colussi, Natasha L. Harvey, Linda M. Shearwin-Whyatt and Sharad Kumar
dc.identifier.citationJournal of Biological Chemistry, 1998; 273(41):26566-26570
dc.identifier.doi10.1074/jbc.273.41.26566
dc.identifier.issn1083-351X
dc.identifier.issn1083-351X
dc.identifier.orcidHarvey, N. [0000-0001-9839-8966]
dc.identifier.orcidShearwin-Whyatt, L. [0000-0002-4504-6534]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/8922
dc.language.isoen
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.rights© 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.source.urihttps://doi.org/10.1074/jbc.273.41.26566
dc.subject3T3 Cells
dc.subjectAnimals
dc.subjectMice
dc.subjectSaccharomyces cerevisiae
dc.subjectEnzyme Precursors
dc.subjectCaspases
dc.subjectLuminescent Proteins
dc.subjectGreen Fluorescent Proteins
dc.subjectRecombinant Fusion Proteins
dc.subjectDNA Primers
dc.subjectApoptosis
dc.subjectProtein Processing, Post-Translational
dc.subjectEnzyme Activation
dc.subjectBase Sequence
dc.subjectDimerization
dc.subjectCaspase 3
dc.subjectCaspase 2
dc.titleConversion of procaspase-3 to an autoactivating caspase by fusion to the caspase-2 predomain
dc.typeJournal article
pubs.publication-statusPublished

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