High impact information on kifunensine

• Kifunensine reduced degradation, suggesting a cooperativity between the glycosylated catalytic domain and the non-glycosylated T peptide [1].
• In addition, ER mannosidase I inhibitor kifunensine and down-regulation of EDEM (ER degradation-enhancing alpha-mannosidase-like protein) also suppressed the degradation of Y611H mutant channels [2].
• To explore the roles of glycosylation in sICAM-1 activity, we expressed sICAM-1 in mutant CHO cell lines differing in glycosylation, including Lec2, Lec8, and Lec1 as well as in CHO cells cultured in the presence of the alpha-mannosidase-I inhibitor kifunensine [3].
• Intriguingly, chronic treatment with kifunensine caused a 3-fold accumulation of Cog Tg in Chinese hamster ovary cells and did not lead to significant induction of the ER unfolded protein response [4].
• Intracellular turnover was arrested with kifunensine, implicating the participation of endoplasmic reticulum mannosidase I in the disposal process [5].

Biological context of kifunensine

• We also found that kifunensine was a poor inhibitor of jack bean and mung bean aryl-alpha-mannosidases, but it was a very potent inhibitor of the plant glycoprotein processing enzyme, mannosidase I (IC50 of 2-5 x 10(-8) M), when [3H]mannose-labeled Man9GlcNAc was used as substrate [6].
• Cultivation of an alpha-1,6-fucosyltransferase (FUT8) knockout Chinese hamster ovary cell line in the presence or absence of a glycosidase inhibitor (either swainsonine or kifunensine) yielded antibody production of each of the three types without contamination by the others [7].
• Twelve of the 38 conformers optimally dock in the active site where the inhibitors 1-deoxymannonojirimycin and kifunensine are found in enzyme crystal structures [8].

Anatomical context of kifunensine

• In addition, natural killer cell lysis of kifunensine-treated cells increases 34% over that of controls [9].
• Studies with rat liver microsomes also indicated that kifunensine inhibited the Golgi mannosidase I, but probably does not inhibit the endoplasmic reticulum mannosidase [6].
• Demonstration that a kifunensine-resistant alpha-mannosidase with a unique processing action on N-linked oligosaccharides occurs in rat liver endoplasmic reticulum and various cultured cells [10].
• Kifunensine also decreased the binding of the labeled acetyl-LDL by the scavenger receptor of the endothelial cells, but the amount of this inhibition relative to controls was significantly less than that of the degradation, suggesting that kifunensine affects two different steps of acetyl-LDL metabolism in these cells [11].
• Studies were undertaken to evaluate the relationship of the recently described (S. Weng and R. G. Spiro, 1993, J. Biol. chem. 268, 25656-25663) rat liver kifunensine (KIF)-resistant mannosidase (ER mannosidase II) to the mannose-trimming enzyme of cytosol [12].

Associations of kifunensine with other chemical compounds

• Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin [13].
• In contrast, kifunensine suppressed ERAD even in castanospermine-treated cells, suggesting that suppression of ERAD does not always require the binding of lectin-like ER chaperones-like calnexin and/or calreticulin [14].

Gene context of kifunensine

• In this paper, the 1.80 A resolution crystal structure of kifunensine bound to Drosophila melanogaster Golgi alpha-mannosidase II (dGMII) is presented [15].
• Monoclonal antibodies to the adhesion molecule LFA-1 and its ligand ICAM-1 reduce lysis of control targets but are less effective in blocking lysis of kifunensine-treated cells [9].

Analytical, diagnostic and therapeutic context of kifunensine

• Kifunensine was tested in cell culture by examining its ability to inhibit processing of the influenza viral glycoproteins in Madin-Darby canine kidney cells [6].

References