Skip to Main content Skip to Navigation
Journal articles

The Ubiquitin specific protease 12 (USP12) is a negative regulator of Notch signaling acting on receptor trafficking towards degradation.

Abstract : Notch signaling is critical for development and adult tissue physiology, controlling cell fate in a context-dependent manner. Upon ligand binding, the transmembrane Notch receptor undergoes two ordered proteolytic cleavages releasing Notch intracellular domain, which regulates the transcription of Notch target genes. Strength of Notch signaling is of crucial importance and depends notably on the quantity of Notch receptor at the cell surface. Using an shRNA library screen monitoring Notch trafficking and degradation in the absence of ligand, we identified mammalian USP12 and its Drosophila melanogaster homolog as novel negative regulators of Notch signaling. USP12 silencing specifically interrupts Notch trafficking to the lysosomes and, as a consequence, leads to an increased amount of receptor at the cell surface and to a higher Notch activity. At the biochemical level, USP12 with its activator UAF1 deubiquitinate the non-activated form of Notch in cell culture and in vitro. These results characterize a new level of conserved regulation of Notch signaling by the ubiquitin system.
Document type :
Journal articles
Complete list of metadatas

Cited literature [29 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-00717028
Contributor : Julien Moretti <>
Submitted on : Tuesday, August 28, 2012 - 6:36:51 PM
Last modification on : Tuesday, September 8, 2020 - 4:48:11 PM
Long-term archiving on: : Thursday, December 15, 2016 - 10:01:37 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

Citation

Julien Moretti, Patricia Chastagner, Chih-Chao Liang, Martin Cohn, Alain Israël, et al.. The Ubiquitin specific protease 12 (USP12) is a negative regulator of Notch signaling acting on receptor trafficking towards degradation.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287, pp.29429-41. ⟨10.1074/jbc.M112.366807⟩. ⟨pasteur-00717028⟩

Share

Metrics

Record views

547