The Ubiquitin Ligase SCF <sup>Fbw7</sup> Antagonizes Apoptotic JNK Signaling
Abdolrahman S. Nateri(The Honourable Society of Lincoln's Inn), Lluı́s Riera-Sans(The Honourable Society of Lincoln's Inn), Clive Da Costa(The Honourable Society of Lincoln's Inn), Axel Behrens(The Honourable Society of Lincoln's Inn)
Cited by 346Open Access
Abstract
Jun N-terminal kinases (JNKs) are essential for neuronal microtubule assembly and apoptosis. Phosphorylation of the activating protein 1 (AP1) transcription factor c-Jun, at multiple sites within its transactivation domain, is required for JNK-induced neurotoxicity. We report that in neurons the stability of c-Jun is regulated by the E3 ligase SCF(Fbw7), which ubiquitinates phosphorylated c-Jun and facilitates c-Jun degradation. Fbw7 depletion resulted in accumulation of phosphorylated c-Jun, stimulation of AP1 activity, and neuronal apoptosis. SCF(Fbw7) therefore antagonizes the apoptotic c-Jun-dependent effector arm of JNK signaling, allowing neurons to tolerate potentially neurotoxic JNK activity.