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The Ubiquitin Ligase SCF Fbw7 Antagonizes Apoptotic JNK Signaling

Year: 2004

Type: article

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.

Source: Science

DOI: 10.1126/science.1092880

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

Institution: Cancer Research UK

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W2138779676

FWCI: 8.277

Cites: 22

Cited by: 346

Related to: 9