Activation of the JNK signaling pathway: Breaking the brake on apoptosis

The JNK signaling pathway is involved in regulation of many cellular events, including growth control, transformation and programmed cell death (apoptosis). The role of JNK activation in apoptosis is highly controversial, being suggested to have a pro‐apoptotic, anti‐apoptotic or no role in this process. It appears that the JNK pathway functions in a cell‐type and stimulus‐dependent manner and its different components can sometimes play opposing roles in apoptosis. Recent studies reveal that the effect of JNK activation on apoptosis depends on the activity of other signaling pathways like the NF‐κB pathway. Here we propose a model that can explain how activation of the JNK pathway “breaks the brake” on apoptosis, thereby regulating, but not initiating the apoptotic process. BioEssays 25:17–24, 2003. © 2002 Wiley Periodicals, Inc.