Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1
Détails
ID Serval
serval:BIB_7A0C6CAC86B2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1
Périodique
Nature
ISSN
0028-0836 (Print)
Statut éditorial
Publié
Date de publication
11/2000
Volume
408
Numéro
6809
Pages
211-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 9
Research Support, Non-U.S. Gov't --- Old month value: Nov 9
Résumé
Cytokines are multifunctional mediators that classically modulate immune activity by receptor-mediated pathways. Macrophage migration inhibitory factor (MIF) is a cytokine that has a critical role in several inflammatory conditions but that also has endocrine and enzymatic functions. The molecular targets of MIF action have so far remained unclear. Here we show that MIF specifically interacts with an intracellular protein, Jab1, which is a coactivator of AP-1 transcription that also promotes degradation of the cyclin-dependent kinase inhibitor p27Kip1 (ref. 10). MIF colocalizes with Jab1 in the cytosol, and both endogenous and exogenously added MIF following endocytosis bind Jab1. MIF inhibits Jab1- and stimulus-enhanced AP-1 activity, but does not interfere with the induction of the transcription factor NFkappaB. Jab1 activates c-Jun amino-terminal kinase (JNK) activity and enhances endogenous phospho-c-Jun levels, and MIF inhibits these effects. MIF also antagonizes Jab1-dependent cell-cycle regulation by increasing p27Kip1 expression through stabilization of p27Kip1 protein. Consequently, Jab1-mediated rescue of fibroblasts from growth arrest is blocked by MIF. Amino acids 50-65 and Cys 60 of MIF are important for Jab1 binding and modulation. We conclude that MIF may act broadly to negatively regulate Jab1-controlled pathways and that the MIF-Jab1 interaction may provide a molecular basis for key activities of MIF.
Mots-clé
Cell Cycle/*physiology
*Cell Cycle Proteins
Cell Line
Cyclin-Dependent Kinase Inhibitor p27
DNA-Binding Proteins/*physiology
Gene Expression Regulation
Hela Cells
Humans
Intracellular Signaling Peptides and Proteins
*JNK Mitogen-Activated Protein Kinases
Luciferases/genetics
MAP Kinase Kinase 4
Macrophage Migration-Inhibitory Factors/*physiology
Microtubule-Associated Proteins/metabolism
Mitogen-Activated Protein Kinase Kinases/metabolism
NF-kappa B/metabolism
Peptide Hydrolases
Precipitin Tests
Protein Binding
Proto-Oncogene Proteins c-jun/metabolism
Recombinant Fusion Proteins/genetics/metabolism
Transcription Factor AP-1/antagonists & inhibitors/*physiology
Transcription Factors/*physiology
*Tumor Suppressor Proteins
Pubmed
Web of science
Création de la notice
25/01/2008 13:35
Dernière modification de la notice
20/08/2019 14:36