tailieunhanh - Báo cáo sinh học: "Functions of O-fucosyltransferase in Notch trafficking and signaling: towards the end of a controversy"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Functions of O-fucosyltransferase in Notch trafficking and signaling: towards the end of a controversy? | Journal of Biology BioMed Central Minireview Functions of O-fucosyltransferase in Notch trafficking and signaling towards the end of a controversy Nicolas Vodovar and Francois Schweisguth Address Ecole Normale Supérieure CNRS UMR8542 46 rue d Ulm 75005 Paris France. Present address Institut Pasteur CNRS URA2578 25 rue du Dr Roux 75015 Paris France. Correspondence Francois Schweisguth. Email schweisg@ Published 28 February 2008 Journal of Biology 2008 7 7 doi jbiol68 The electronic version of this article is the complete one and can be found online at http content 7 2 7 2008 BioMed Central Ltd Abstract The precise role of the O-fucosyltransferase Ofutl in Notch-receptor trafficking has remained controversial. A recent study sheds new light on the non-catalytic activity of Ofut1 and provides further evidence that Ofut1 acts as a chaperone in the endoplasmic reticulum. Notch proteins are evolutionarily conserved cell-surface receptors for transmembrane ligands of the DSL family named after the Delta and Serrate ligands of Drosophila 1 2 . Signaling by Notch regulates a broad range of cell-fate decisions during development and various human diseases including cancers have been associated with defects in Notch signaling. The extracellular part of Notch contains 36 epidermal growth factor-like EGF repeats carrying the ligand-binding region and three Lin12 Notch repeats LNRs that limit proteolytic cleavage of the receptor at the S2 site and hence limit its activation 2 . The EGF repeats are modified by two types of O-linked glycosylation O-glucosylation and O-fuco-sylation Figure 1a both are important for Notch activity 3-6 Figure 1a . O-fucosylation of Notch is catalyzed by an O-fucosyl-transferase Pofut1 in mammals and Ofut1 in Drosophila 7 8 that uses GDP-fucose as a substrate. The O-fucose residue added by this O-fucosyltransferase can be further elongated by the addition of an N-acetylglucosamine by Fringe an EGF-O-fucose P1 3 .