JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins

Targeted gene disruption studies have established that the c‐Jun NH2‐terminal kinase (JNK) is required for the stress‐induced release of mitochondrial cytochrome c and apoptosis, and that the Bax subfamily of Bcl‐2‐related proteins is essential for JNK‐dependent apoptosis. However, the mechanism by which JNK regulates Bax has remained unsolved. Here we demonstrate that activated JNK promotes Bax translocation to mitochondria through phosphorylation of 14‐3‐3, a cytoplasmic anchor of Bax. Phosphorylation of 14‐3‐3 led to dissociation of Bax from this protein. Expression of phosphorylation‐defective mutants of 14‐3‐3 blocked JNK‐induced Bax translocation to mitochondria, cytochrome c release and apoptosis. Collectively, these results have revealed a key mechanism of Bax regulation in stress‐induced apoptosis.