Document Detail

The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling.
MedLine Citation:
PMID:  14739463     Owner:  NLM     Status:  MEDLINE    
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.
Abdolrahman S Nateri; Lluís Riera-Sans; Clive Da Costa; Axel Behrens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-01-22
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  303     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-27     Completed Date:  2004-03-18     Revised Date:  2011-05-23    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1374-8     Citation Subset:  IM    
Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Cell Cycle Proteins / genetics,  metabolism*
Cell Line
F-Box Proteins / genetics,  metabolism*
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Mitogen-Activated Protein Kinases / metabolism*
Molecular Sequence Data
Neurons / physiology*
PC12 Cells
Proto-Oncogene Proteins c-jun / metabolism*
RNA, Small Interfering / metabolism
Transcription Factor AP-1 / metabolism
Ubiquitin / metabolism
Ubiquitin-Protein Ligases / genetics,  metabolism*
Reg. No./Substance:
0/Cell Cycle Proteins; 0/F-Box Proteins; 0/Fbxw7 protein, mouse; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Small Interfering; 0/Transcription Factor AP-1; 0/Ubiquitin; EC Mitogen-Activated Protein Kinases; EC Protein Kinases; EC protein, human; EC Ligases

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