Abstract
The biological activities of macrophage migration inhibitory factor (MIF) might be mediated through a classical receptormediated or non-classical endocytic pathway. JAB1 (C-Jun activation domain-binding protein-1) promotes the degradation of the tumor suppressor, p53, and the cyclin-dependent kinase inhibitor, p27. When MIF and JAB1 are bound to each other in various intracellular sites, MIF inhibits the positive regulatory effects of JAB1 on the activity of AP-1. The intestinal parasite, Anisakis simplex, has an immunomodulatory effect. The molecular mechanism of action of As-MIF and human JAB1 are poorly understood. In this study, As-MIF and hJAB1 were expressed and purified with high solubility. The structure of As-MIF and hJAB1 interaction was modeled by homology modeling based on the structure of Ace-MIF. This study provides evidence indicating that the MIF domain of As-MIF interacts directly with the MPN domain of hJAB1, and four structure-based mutants of As-MIF and hJAB1 disrupt the As-MIF-hJAB1 interaction. [BMB Reports 2017; 50(5): 269-274].
MeSH terms
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Amino Acid Sequence
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COP9 Signalosome Complex / metabolism*
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COP9 Signalosome Complex / physiology
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Cell Cycle Checkpoints
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism*
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Intracellular Signaling Peptides and Proteins / physiology
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Intramolecular Oxidoreductases / metabolism*
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Intramolecular Oxidoreductases / physiology
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Macrophage Migration-Inhibitory Factors / metabolism*
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Macrophage Migration-Inhibitory Factors / physiology
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Peptide Hydrolases / metabolism*
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Peptide Hydrolases / physiology
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Protein Binding
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Protein Domains
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Protein Structural Elements / physiology
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Transcription Factor AP-1 / metabolism
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Tumor Suppressor Protein p53 / metabolism
Substances
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Cell Cycle Proteins
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Intracellular Signaling Peptides and Proteins
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Macrophage Migration-Inhibitory Factors
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Transcription Factor AP-1
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Tumor Suppressor Protein p53
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Cyclin-Dependent Kinase Inhibitor p27
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Peptide Hydrolases
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COPS5 protein, human
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COP9 Signalosome Complex
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Intramolecular Oxidoreductases
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MIF protein, human