The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling

  • Science. 2004 Feb 27;303(5662):1374-8. doi: 10.1126/science.1092880.
Abdolrahman S Nateri  1 ,  Lluís Riera-Sans ,  Clive Da Costa ,  Axel Behrens
Affiliations
  • 1. Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
PMID: 14739463 DOI: 10.1126/science.1092880
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.