The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses
Figure 4
Bcl-2 family in apoptosis. (a) The domain structure of three classes of Bcl-2 family proteins. Antiapoptotic Bcl-2-like proteins have four Bcl-2 homology (BH) domains and a C-terminal transmembrane domain. Proapoptotic Bcl-2 family proteins are classified into two groups. Bax-like proteins have three BH domains (BH1-BH3) and a C-terminal transmembrane domain. Proapoptotic proteins, such as BID, BAD, NOXA, and PUMA, only have a BH3 domain and thus are called BH3-only proteins; some BH-3-only proteins, such as BIK, have a C-terminal transmembrane domain. (b) Survival signals suppress apoptosis by promoting the phosphorylation of BAD at Ser112, Ser136, and Ser155. When these sites are phosphorylated, BAD binds to 14-3-3 proteins, which suppresses the proapoptotic activity of BAD by inhibiting its association with antiapoptotic proteins such as Bcl-2. During apoptosis, dephosphorylated BAD dimerizes with Bcl-xL or Bcl-2 and promotes the release of inner mitochondrial proteins such as cytochrome c (Cyt c) through pores formed by BAX.
