The Ubiquitin Ligase SCF Fbw7 Antagonizes Apoptotic JNK Signaling
- 27 February 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 303 (5662) , 1374-1378
- https://doi.org/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 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.Keywords
This publication has 21 references indexed in Scilit:
- The SCF Ubiquitin Ligase: An Extended LookMolecular Cell, 2002
- AP-1 as a regulator of cell life and deathNature Cell Biology, 2002
- A System for Stable Expression of Short Interfering RNAs in Mammalian CellsScience, 2002
- Phosphorylation-Dependent Ubiquitination of Cyclin E by the SCF Fbw7 Ubiquitin LigaseScience, 2001
- Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell lineNature, 2001
- Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell linesNature, 2001
- Signal Transduction by the JNK Group of MAP KinasesPublished by Elsevier ,2000
- SCF and Cullin/RING H2-Based Ubiquitin LigasesAnnual Review of Cell and Developmental Biology, 1999
- Identification of a family of human F-box proteinsCurrent Biology, 1999
- Reduced Ubiquitin-Dependent Degradation of c-Jun After Phosphorylation by MAP KinasesScience, 1997