Role for Bcl-xLas an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis

Surender Kharbanda; Pramod S. Pandey; Lesley Schofield; Sara J. Israels; Richard Roncinske; Kiyotsugu Yoshida; Ajit Bharti; Zhi-Min Yuan; Satya Saxena; Ralph R. Weichselbaum; Carlo M. Nalin; Donald Küfe

doi:10.1073/pnas.94.13.6939

Abstract

Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-2-related protein Bcl-x L fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress. Coimmunoprecipitation studies demonstrate that Bcl-x L associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-x L and not to the proapoptotic Bcl-x s protein. The results also demonstrate that Bcl-x s blocks binding of cytochrome C to Bcl-x L . Our findings support a role for Bcl-x L in protecting cells from apoptosis by inhibiting the availability of cytochrome C in the cytosol.

Keywords

Cytochrome cCytosolCytochromeApoptosisApoptosomeBcl-xLCytochrome bImmunoprecipitationBiologyCell biologyMitochondrionCytochrome P450 reductaseProgrammed cell deathMolecular biologyBiochemistryCoenzyme Q – cytochrome c reductaseMitochondrial DNACaspaseEnzymeGene

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Publication Info

Year: 1997
Type: article
Volume: 94
Issue: 13
Pages: 6939-6942
Citations: 396
Access: Closed

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APA Style

                            
                                
                                    Surender Kharbanda, 
                                
                                    Pramod S. Pandey, 
                                
                                    Lesley Schofield
                                
                                et al.
                            
                            (1997). 
                            Role for Bcl-x<sub>L</sub>as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis. 
                            Proceedings of the National Academy of Sciences
                            , 94
                            (13)
                            , 6939-6942.
                            https://doi.org/10.1073/pnas.94.13.6939
                        

Identifiers

DOI: 10.1073/pnas.94.13.6939