title: Structural characterization of As-MIF and hJAB1 during the inhibition of cell-cycle regulation.
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].
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea.
authors.forename: Mi Suk
authors.initials: MS
authors.lastname: Jeong
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Centre for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.affiliation: Department of Parasitology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Hak Sun
authors.initials: HS
authors.lastname: Yu
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea.
authors.forename: Se Bok
authors.initials: SB
authors.lastname: Jang
mesh_terms: D000595:Amino Acid Sequence; D000075686:COP9 Signalosome Complex / Q000378:metabolism* / Q000502:physiology; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism* / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism* / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D000072417:Protein Domains; D000072416:Protein Structural Elements / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008263:Macrophage Migration-Inhibitory Factors; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human