Publication Date:
2004-01-24
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nateri, Abdolrahman S -- Riera-Sans, Lluis -- Da Costa, Clive -- Behrens, Axel -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1374-8. Epub 2004 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14739463" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
*Apoptosis
;
Base Sequence
;
Cell Cycle Proteins/genetics/*metabolism
;
Cell Line
;
F-Box Proteins/genetics/*metabolism
;
Humans
;
JNK Mitogen-Activated Protein Kinases
;
MAP Kinase Signaling System
;
Mice
;
Mitogen-Activated Protein Kinases/*metabolism
;
Molecular Sequence Data
;
Neurons/*physiology
;
PC12 Cells
;
Phosphorylation
;
Proto-Oncogene Proteins c-jun/*metabolism
;
RNA, Small Interfering/metabolism
;
Rats
;
Transcription Factor AP-1/metabolism
;
Transfection
;
Ubiquitin/metabolism
;
Ubiquitin-Protein Ligases/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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