Conversion of Bcl-2 to a Bax-like Death Effector by Caspases

Abstract

Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). The loop domain of Bcl-2 is cleaved at Asp 34 by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. The carboxyl-terminal Bcl-2 cleavage product triggered cell death and accelerated Sindbis virus–induced apoptosis, which was dependent on the BH3 homology and transmembrane domains of Bcl-2. Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. Cleavage-resistant mutants of Bcl-2 had increased protection from interleukin-3 withdrawal and Sindbis virus–induced apoptosis. Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death.

Keywords

CaspaseApoptosisProgrammed cell deathCell biologyProteasesSindbis virusCleavage (geology)Intrinsic apoptosisNLRP1BiologyChemistryBiochemistryEnzymeGene

MeSH Terms

AnimalsApoptosisCOS CellsCaspase 3CaspasesCell LineCysteine EndopeptidasesCysteine Proteinase InhibitorsEnzyme ActivationHumansInterleukin-3Jurkat CellsMutationProtein StructureSecondaryProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Recombinant ProteinsSindbis VirusTransfectionbcl-2-Associated X Proteinfas Receptor

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Publication Info

Year: 1997
Type: article
Volume: 278
Issue: 5345
Pages: 1966-1968
Citations: 1109
Access: Closed

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APA Style

                            
                                
                                    Emily H. Cheng, 
                                
                                    David G. Kirsch, 
                                
                                    Rollie J. Clem
                                
                                et al.
                            
                            (1997). 
                            Conversion of Bcl-2 to a Bax-like Death Effector by Caspases. 
                            Science
                            , 278
                            (5345)
                            , 1966-1968.
                            https://doi.org/10.1126/science.278.5345.1966
                        

Identifiers

DOI: 10.1126/science.278.5345.1966
PMID: 9395403

Data Quality

Data completeness: 81%