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dc.creatorGlavic,Alvaro
dc.creatorLópez-Varea,Ana
dc.creatorde Celis,José F
dc.date2011-01-01
dc.date.accessioned2019-05-02T21:21:59Z
dc.date.available2019-05-02T21:21:59Z
dc.identifierhttps://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100004
dc.identifier.urihttp://revistaschilenas.uchile.cl/handle/2250/82107
dc.descriptionThe Notch signaling pathway plays an important role in development and physiology. In Drosophila, Notch is activated by its Delta or Serrate ligands, depending in part on the sugar modifications present in its extracellular domain. O-fucosyltransferase-1 (OFUT1) performs the first glycosylation step in this process, O-fucosylating various EGF repeats at the Notch extracellular domain. Besides its O-fucosyltransferase activity, OFUT1 also behaves as a chaperone during Notch synthesis and is able to down regulate Notch by enhancing its endocytosis and degradation. We have reevaluated the roles that O-fucosylation and the synthesis of GDP-fucose play in the regulation of Notch protein stability. Using mutants and the UAS/Gal4 system, we modified in developing tissues the amount of GDP-mannose-deshydratase (GMD), the first enzyme in the synthesis of GDP-fucose. Our results show that GMD activity, and likely the levels of GDP-fucose and O-fucosylation, are essential to stabilize the Notch protein. Notch degradation observed under low GMD expression is absolutely dependent on OFUT1 and this is also observed in Notch Abruptex mutants, which have mutations in some potential O-fucosylated EGF domains. We propose that the GDP-fucose/OFUT1 balance determines the ability of OFUT1 to endocytose and degrade Notch in a manner that is independent of the residues affected by Abruptex mutations in Notch EGF domains.
dc.formattext/html
dc.languageen
dc.publisherSociedad de Biología de Chile
dc.relation10.4067/S0716-97602011000100004
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourceBiological Research v.44 n.1 2011
dc.subjectNotch
dc.subjectGMD
dc.subjectO-fucosyltranserase
dc.subjectDrosophila
dc.titleThe balance between GMD and OFUT1 regulates Notch signaling pathway activity by modulating Notch stability


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