Two independent positive feedbacks and bistability in the Bcl-2 apoptotic switch.

ABSTRACT:

Background

The complex interplay between B-cell lymphoma 2 (Bcl-2) family proteins constitutes a crucial checkpoint in apoptosis. Its detailed molecular mechanism remains controversial. Our former modeling studies have selected the 'Direct Activation Model' as a better explanation for experimental observations. In this paper, we continue to extend this model by adding interactions according to updating experimental findings.

Methodology/principal findings

Through mathematical simulation we found bistability, a kind of switch, can arise from a positive (double negative) feedback in the Bcl-2 interaction network established by anti-apoptotic group of Bcl-2 family proteins. Moreover, Bax/Bak auto-activation as an independent positive feedback can enforce the bistability, and ma

SUBMITTER: Cui J 

PROVIDER: S-EPMC2194625 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature