New molecular medicine findings from Stony Brook University, Institute for Cell and Developmental Biology described
2007 JUL 10 -- Fresh data on molecular medicine are presented in the report "Notch signaling in normal and disease States: possible therapies related to glycosylation. The Notch signaling pathway is involved in a wide variety of highly conserved developmental processes in mammals. Importantly, mutations of the Notch protein and components of its signaling pathway have been implicated in an array of human diseases (T-cell leukemia and other cancers, Multiple Sclerosis, CADASIL, Alagille Syndrome, Spondylocostal Dysostosis)," scientists writing in the journal Current Molecular Medicine report. "In mammals, Notch becomes activated upon binding of its extracellular domain to ligands (Delta and Jagged/Serrate) that are present on the surface of apposed cells. The extracellular domain of Notch contains up to 36 tandem Epidermal Growth Factor-like (EGF) repeats. Many of these EGF repeats are modified at evolutionarily-conserved consensus sites by an unusual form of O-glycosylation called O-fucose. Work from several groups indicates that O-fucosylation plays an important role in ligand mediated Notch signaling. Recent evidence also suggests that the enzyme responsible for addition of O-fucose to Notch, protein O-fucosyltransferase-1 (POFUT1), may serve a quality control function in the endoplasmic reticulum. Additionally, some of the O-fucose moieties are further elongated by the action of members of the Fringe family of beta-1,3-N-acetylglucosaminyltransferases. The alteration in O-fucose saccharide structure caused by Fringe modulates the response of Notch to its ligands. Thus, glycosylation serves an important role in regulating Notch activity. This review focuses on the role of glycosylation in the normal functioning of the Notch pathway," wrote R. Rampal and colleagues, Stony Brook University, Institute for Cell and Developmental Biology. The researchers concluded: "As well, potential roles for glycosylation in Notch-related human diseases, and possible roles for therapeutic targeting of POFUT1 and Fringe in Notch-related human diseases, are discussed." Rampal and colleagues published their study in Current Molecular Medicine (Notch signaling in normal and disease States: possible therapies related to glycosylation. Current Molecular Medicine, 2007;7(4):427-45). Additional information can be obtained by contacting R. Rampal, Institute for Cell and Developmental Biology, Dept. of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, 11794-5215 USA. The publisher of the journal Current Molecular Medicine can be contacted at: Bentham Science Publ Ltd., Executive Ste. Y26, PO Box 7917, Saif Zone, 1200 Br Sharjah, U Arab Emirates. Keywords: United States, Stony Brook, Molecular Medicine. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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