c-Myc Functionally Cooperates with Bax To Induce Apoptosis

AUTOR(ES)

Juin, Philippe

FONTE

American Society for Microbiology

RESUMO

c-Myc promotes apoptosis by destabilizing mitochondrial integrity, leading to the release of proapoptotic effectors including holocytochrome c. Candidate mediators of c-Myc in this process are the proapoptotic members of the Bcl-2 family. We show here that fibroblasts lacking Bak remain susceptible to c-Myc-induced apoptosis whereas bax-deficient fibroblasts are resistant. However, despite this requirement for Bax, c-Myc activation exerts no detectable effects on Bax expression, localization, or conformation. Moreover, susceptibility to c-Myc-induced apoptosis can be restored in bax-deficient cells by ectopic expression of Bax or by microinjection of a peptide comprising a minimal BH3 domain. Microinjection of BH3 peptide also restores sensitivity to c-Myc-induced apoptosis in p53-deficient primary fibroblasts that are otherwise resistant. By contrast, there is no synergy between BH3 peptide and c-Myc in fibroblasts deficient in both Bax and Bak. We conclude that c-Myc triggers a proapoptotic mitochondrial destabilizing activity that cooperates with proapoptotic members of the Bcl-2 family.

Documentos Relacionados

• c-Myc cooperates with activated Ras to induce the cdc2 promoter.
• Novel targeted deregulation of c-Myc cooperates with Bcl-XL to cause plasma cell neoplasms in mice
• Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT)
• N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation
• c-Myc Augments Gamma Irradiation-Induced Apoptosis by Suppressing Bcl-XL