Linked Life Data

19567869

Source:http://linkedlifedata.com/resource/pubmed/id/19567869

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2009-9-21
pubmed:abstractText
Notch is a transmembrane receptor that controls cell fate decisions during development and tissue homeostasis. Both activation and attenuation of the Notch signal are tightly regulated by endocytosis. The adaptor protein Numb acts as an inhibitor of Notch and is known to function within the intracellular trafficking pathways. However, a role for Numb in regulating Notch trafficking has not been defined. Here we show that mammalian Notch1 is constitutively internalized and trafficked to both recycling and late endosomal compartments, and we demonstrate that changes in Numb expression alter the dynamics of Notch1 trafficking. Overexpression of Numb promotes sorting of Notch1 through late endosomes for degradation, whereas depletion of Numb facilitates Notch1 recycling. Numb mutants that do not interact with the ubiquitin-protein isopeptide ligase, Itch, or that lack motifs important for interaction with endocytic proteins fail to promote Notch1 degradation. Our data suggest that Numb inhibits Notch1 activity by regulating post-endocytic sorting events that lead to Notch1 degradation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26427-38
pubmed:dateRevised
2010-9-29
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Numb regulates post-endocytic trafficking and degradation of Notch1.
pubmed:affiliation
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural