Abstract:
: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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Juin P,Hunt A,Littlewood T,Griffiths B,Swigart LB,Korsmeyer S,Evan Gdoi
10.1128/mcb.22.17.6158-6169.2002subject
Has Abstractpub_date
2002-09-01 00:00:00pages
6158-69issue
17eissn
0270-7306issn
1098-5549journal_volume
22pub_type
杂志文章abstract::The abundance of the mRNA for human triosephosphate isomerase (TPI) is decreased to approximately 20% of normal by frameshift and nonsense mutations that cause translation to terminate at a nonsense codon within the first three-fourths of the reading frame. Results of previous studies inhibiting RNA synthesis with act...
journal_title:Molecular and cellular biology
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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