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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2003-9-1
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pubmed:abstractText |
Macrophage migration inhibitory factor (MIF) is a cytokine that participates in the host inflammatory response. A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein oxidoreductase activity of MIF is associated with certain biological functions. Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some biochemical properties of the full-length protein. We report on the characterization of CXXC-spanning MIF-(50-65) and its serine variant, C57S/C60S-MIF-(50-65). Following disulfide-mediated cyclization, MIF-(50-65) adapted a beta-turn conformation comparable with that of beta-turn-containing cyclo-57,60-[Asp57,Dap60]MIF-(50-65). MIF-(50-65) had a redox potential E'0 of -0.258 V and formed mixed disulfides with glutathione and cysteine. MIF-(50-65) but not C57S/C60S-MIF-(50-65) had oxidoreductase activity in vitro. Intriguingly, MIF-(50-65) exhibited MIF-like cellular activities. The peptide but not its variant had glucocorticoid overriding and proliferation-enhancing activity and stimulated ERK1/2 phosphorylation. MIF-(50-65) and its variant bound to the MIF-binding protein JAB1 and enhanced cellular levels of p27Kip1. As the peptide and its variant were endocytosed at similar efficiency, sequence 50-65 appears sufficient for the JAB1-related effects of MIF, whereas other activities require CXXC. Cyclo-57,60-[Asp57,Dap60]MIF-(50-65) activated ERK1/2, indicating that CXXC-dependent disulfide and beta-turn formation is associated with an activity-inducing conformation. We conclude that CXXC and sequence 50-65 are critical for the activities of MIF. MIF-(50-65) is a surprisingly short sequence with MIF-like functions that could be an excellent molecular template for MIF therapeutics.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Migration-Inhibitory...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33654-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12796500-3T3 Cells,
pubmed-meshheading:12796500-Amino Acid Motifs,
pubmed-meshheading:12796500-Amino Acid Sequence,
pubmed-meshheading:12796500-Animals,
pubmed-meshheading:12796500-Biotinylation,
pubmed-meshheading:12796500-Catalysis,
pubmed-meshheading:12796500-Cell Cycle Proteins,
pubmed-meshheading:12796500-Cell Division,
pubmed-meshheading:12796500-Cells, Cultured,
pubmed-meshheading:12796500-Chromatography, High Pressure Liquid,
pubmed-meshheading:12796500-Circular Dichroism,
pubmed-meshheading:12796500-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:12796500-Cysteine,
pubmed-meshheading:12796500-Disulfides,
pubmed-meshheading:12796500-Endocytosis,
pubmed-meshheading:12796500-Endothelium, Vascular,
pubmed-meshheading:12796500-Glutathione,
pubmed-meshheading:12796500-Humans,
pubmed-meshheading:12796500-Inflammation,
pubmed-meshheading:12796500-Kinetics,
pubmed-meshheading:12796500-Macrophage Migration-Inhibitory Factors,
pubmed-meshheading:12796500-Mass Spectrometry,
pubmed-meshheading:12796500-Mice,
pubmed-meshheading:12796500-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12796500-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12796500-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12796500-Molecular Sequence Data,
pubmed-meshheading:12796500-Oxidation-Reduction,
pubmed-meshheading:12796500-Oxygen,
pubmed-meshheading:12796500-Peptides,
pubmed-meshheading:12796500-Phosphorylation,
pubmed-meshheading:12796500-Protein Binding,
pubmed-meshheading:12796500-Protein Conformation,
pubmed-meshheading:12796500-Serine,
pubmed-meshheading:12796500-Signal Transduction,
pubmed-meshheading:12796500-Sulfhydryl Compounds,
pubmed-meshheading:12796500-Time Factors,
pubmed-meshheading:12796500-Tumor Suppressor Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
A 16-residue peptide fragment of macrophage migration inhibitory factor, MIF-(50-65), exhibits redox activity and has MIF-like biological functions.
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pubmed:affiliation |
Division of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital RWTH Aachen, D-52074 Aachen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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