Skip to Main content Skip to Navigation
Journal articles

Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptor.

Abstract : Activation of mammalian Notch receptor by its ligands induces TNFalpha-converting enzyme-dependent ectodomain shedding, followed by intramembrane proteolysis due to presenilin (PS)-dependent gamma-secretase activity. Here, we demonstrate that a new modification, a monoubiquitination, as well as clathrin-dependent endocytosis, is required for gamma-secretase processing of a constitutively active Notch derivative, DeltaE, which mimics the TNFalpha-converting enzyme-processing product. PS interacts with this modified form of DeltaE, DeltaEu. We identified the lysine residue targeted by the monoubiquitination event and confirmed its importance for activation of Notch receptor by its ligand, Delta-like 1. We propose a new model where monoubiquitination and endocytosis of Notch are a prerequisite for its PS-dependent cleavage, and discuss its relevance for other gamma-secretase substrates.
Document type :
Journal articles
Complete list of metadatas

Cited literature [66 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-00583271
Contributor : Neetu Gupta-Rossi <>
Submitted on : Tuesday, April 5, 2011 - 1:23:03 PM
Last modification on : Monday, February 3, 2020 - 6:02:15 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Neetu Gupta-Rossi, Emmanuelle Six, Odile Lebail, Frédérique Logeat, Patricia Chastagner, et al.. Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptor.. Journal of Cell Biology, Rockefeller University Press, 2004, 166 (1), pp.73-83. ⟨10.1083/jcb.200310098⟩. ⟨pasteur-00583271⟩

Share

Metrics

Record views

174