Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea.
Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Centre for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
BMB Rep. 2017 May;50(5):269-274. doi: 10.5483/bmbrep.2017.50.5.201.
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].
巨噬细胞移动抑制因子（MIF）的生物学活性可能通过经典的受体介导或非经典的内吞途径来介导。JAB1（C-Jun 激活区结合蛋白-1）促进肿瘤抑制因子 p53 和细胞周期蛋白依赖性激酶抑制剂 p27 的降解。当 MIF 和 JAB1 在各种细胞内位置结合在一起时，MIF 抑制 JAB1 对 AP-1 活性的正向调节作用。肠道寄生虫 Anisakis simplex 具有免疫调节作用。As-MIF 和人 JAB1 的作用分子机制尚不清楚。在这项研究中，As-MIF 和 hJAB1 以高溶解度表达和纯化。基于 Ace-MIF 的结构，通过同源建模对 As-MIF 和 hJAB1 相互作用的结构进行了建模。这项研究提供了证据表明，As-MIF 的 MIF 结构域与 hJAB1 的 MPN 结构域直接相互作用，并且 As-MIF 和 hJAB1 的四个基于结构的突变体破坏了 As-MIF-hJAB1 的相互作用。[BMB 报告 2017；50(5): 269-274]。
