Реферат: The extracellular domain of Notch contains epidermal growth factor (EGF) repeats that are extensively modified with different O-linked glycans. O-Fucosylation is essential for receptor function, and elongation with N-acetylglucosamine, catalyzed by members of the Fringe family, modulates Notch activity. Only recently, genes encoding enzymes involved in the O-glucosylation pathway have been cloned. In the Drosophila mutant rumi, characterized by a mutation in the protein O-glucosyltransferase, Notch signaling is impaired in a temperature-dependent manner, and a mouse knock-out leads to embryonic lethality. We have previously identified two human genes, GXYLT1 and GXYLT2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to O-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene C3ORF21 encodes a UDP-xylose:α-xyloside α1,3-xylosyltransferase, acting on xylose-α1,3-glucoseβ1-containing acceptor structures. We have, therefore, renamed it XXYLT1 (xyloside xylosyltransferase 1). XXYLT1 cannot act on a synthetic acceptor containing an α-linked xylose alone, but requires the presence of the underlying glucose. Activity on Notch EGF repeats was proven by in vitro xylosylation of a mouse Notch1 fragment recombinantly produced in Sf9 insect cells, a bacterially expressed EGF repeat from mouse Notch2 modified in vitro by Rumi and Gxylt2 and in vivo by co-expression of the enzyme with the Notch1 fragment. The enzyme was shown to be a typical type II membrane-bound glycosyltransferase localized in the endoplasmic reticulum.

Библиографическая ссылка: Sethi M.K. , Buettner F.F.R. , Ashikov A. , Krylov V.B. , Takeuchi H. , Nifantiev N.E. , Haltiwanger R.S. , Gerardy-Schahn R. , Bakker H.
Molecular Cloning of a Xylosyltransferase That Transfers the Second Xylose to O-Glucosylated Epidermal Growth Factor Repeats of Notch
Journal of Biological Chemistry. 2012. V.287. N4. P.2739-2748. DOI: 10.1074/jbc.m111.302406 WOS Scopus OpenAlex

Идентификаторы БД:

≡ Web of science:	WOS:000300292300045
≡ Scopus:	2-s2.0-84856070820
≡ OpenAlex:	W2071786488

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