Biological consequences of overexpressing or eliminating N-acetylglucosaminyltransferase-TIII in the mouse.
N-acetylglucosaminyltransferase III (GlcNAc-TIII), a product of the human MGAT3 gene, was discovered as a glycosyltransferase activity in hen oviduct. GlcNAc-TIII transfers GlcNAc in beta4-linkage to the core Man of complex or hybrid N-glycans, and thereby alters not only the composition, but also the conformation of the N-glycan. The dramatic consequences of the addition of this bisecting GlcNAc residue are reflected in the altered binding of lectins that recognize Gal residues on N-glycans. Changes in GlcNAc-TIII expression correlate with hepatoma and leukemia in rodents and humans, and the bisecting GlcNAc on Asn 297 of human IgG antibodies enhances their effector functions. Overexpression of a cDNA encoding GlcNAc-TIII alters growth control and cell-cell interactions in cultured cells, and in transgenic mice. While mice lacking GlcNAc-TIII are viable and fertile, they exhibit retarded progression of diethylnitrosamine (DEN)-induced liver tumors. Further biological functions of GlcNAc-TIII are expected to be uncovered as mice with a null mutation in the Mgat3 gene are challenged.
Stanley
Pamela
P
Department of Cell Biology, Albert Einstein College Medicine, Yeshiva University, Bronx, New York, NY 10461, USA. stanley@aecom.yu.edu
D000818:Animals; D002450:Cell Communication; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000502:physiology*
D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase