Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1

Details

Serval ID
serval:BIB_7A0C6CAC86B2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1
Journal
Nature
Author(s)
Kleemann  R., Hausser  A., Geiger  G., Mischke  R., Burger-Kentischer  A., Flieger  O., Johannes  F. J., Roger  T., Calandra  T., Kapurniotu  A., Grell  M., Finkelmeier  D., Brunner  H., Bernhagen  J.
ISSN
0028-0836 (Print)
Publication state
Published
Issued date
11/2000
Volume
408
Number
6809
Pages
211-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 9
Abstract
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.
Keywords
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
Create date
25/01/2008 13:35
Last modification date
20/08/2019 14:36
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