Blockade of the BAK hydrophobic groove by inhibitory phosphorylation regulates commitment to apoptosis.

ABSTRACT: The BCL-2 family protein BAK is a key regulator of mitochondrial apoptosis. BAK activation first involves N-terminal conformational changes that lead to the transient exposure of the BAK BH3 domain that then inserts into a hydrophobic groove on another BAK molecule to form symmetric dimers. We showed recently that post-translational modifications are important in the regulation of BAK conformational change and multimerization, with dephosphorylation at tyrosine 108 constituting an initial step in the BAK activation process. We now show that dephosphorylation of serine 117 (S117), located in the BAK hydrophobic groove, is also critical for BAK activation to proceed to completion. Phosphorylation of BAK at S117 has two important regulatory functions: first, it occludes the binding of BH3-con

SUBMITTER: Azad A 

PROVIDER: S-EPMC3506661 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature