The Ubiquitin Ligase SCF Fbw7 Antagonizes Apoptotic JNK Signaling

Nateri, Abdolrahman S.; Riera-Sans, Lluís; Da Costa, Clive; Behrens, Axel

Abstract

Jun N-terminal kinases (JNKs) are essential for neuronal microtubute 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 SCFFbw7, 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. SCFFbw7 therefore antagonizes the apoptotic c-Jun-dependent effector arm of JNK signaling, allowing neurons to tolerate potentially neurotoxic JNK activity.

Citation

Nateri, A. S., Riera-Sans, L., Da Costa, C., & Behrens, A. (2004). The Ubiquitin Ligase SCF Fbw7 Antagonizes Apoptotic JNK Signaling. Science, 303(5662), 1374-1378. https://doi.org/10.1126/science.1092880

• Journal Article Type: Article
• Acceptance Date: Jan 8, 2004
• Publication Date: Feb 27, 2004
• Deposit Date: Sep 11, 2024
• Journal: Science
• Print ISSN: 0036-8075
• Electronic ISSN: 1095-9203
• Publisher: American Association for the Advancement of Science
• Peer Reviewed: Peer Reviewed
• Volume: 303
• Issue: 5662
• Pages: 1374-1378
• DOI: https://doi.org/10.1126/science.1092880
• Public URL: https://nottingham-repository.worktribe.com/output/39458173
• Publisher URL: https://www.science.org/doi/10.1126/science.1092880