Cellular damage signals promote sequential changes at the N-terminus and BH-1 domain of the pro-apoptotic protein Bak.
Oncogene
; 20(52): 7668-76, 2001 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-11753644
ABSTRACT
The pro-apoptotic protein Bak is converted from a latent to an active form by damage-induced signals. This process involves an early exposure of an occluded N-terminal epitope of Bak in intact cells. Here we report a subsequent damage-induced change in Bak, detected using an antibody to the central BH-1 domain. Bak co-immunoprecipitated with Bc1-x(L) both in undamaged cells and early after damage, when the N-terminal epitope was exposed but the BH-1 epitope remained occluded. A subsequent decrease in binding of Bak to Bc1-x(L) correlated with exposure of an epitope in the Bak BH-1 domain. Overexpression of Bc1-x(L) did not affect the kinetics of exposure of the Bak N-terminal epitope but delayed exposure of the BH-1 domain. Cytochrome c release from mitochondria facilitates the activation of apoptotic caspases. The majority of cells with exposed Bak BH-1 domains contained cytosolic cytochrome c. However, a small proportion of cells exhibited exposed Bak BH-1 domains that co-localized with mitochondrial cytochrome c. The data are consistent with a two-step model for the activation of Bak by drug-induced damage signals where dissociation of Bc1-x(L) from the BH-1 domain of Bak occurs immediately prior to or concomitantly with cytochrome c release.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Apoptose
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article