Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. - Institut Pasteur Access content directly
Journal Articles Journal of Biological Chemistry Year : 2001

Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor.

Abstract

The Notch signaling pathway is essential in many cell fate decisions in invertebrates as well as in vertebrates. After ligand binding, a two-step proteolytic cleavage releases the intracellular part of the receptor which translocates to the nucleus and acts as a transcriptional activator. Although Notch-induced transcription of genes has been reported extensively, its endogenous nuclear form has been seldom visualized. We report that the nuclear intracellular domain of Notch1 is stabilized by proteasome inhibitors and is a substrate for polyubiquitination in vitro. SEL-10, an F-box protein of the Cdc4 family, was isolated in a genetic screen for Lin12/Notch-negative regulators in Caenorhabditis elegans. We isolated human and murine counterparts of SEL-10 and investigated the role of a dominant-negative form of this protein, deleted of the F-box, on Notch1 stability and activity. This molecule could stabilize intracellular Notch1 and enhance its transcriptional activity but had no effect on inactive membrane-anchored forms of the receptor. We then demonstrated that SEL-10 specifically interacts with nuclear forms of Notch1 and that this interaction requires a phosphorylation event. Taken together, these data suggest that SEL-10 is involved in shutting off Notch signaling by ubiquitin-proteasome-mediated degradation of the active transcriptional factor after a nuclear phosphorylation event.
Embargoed file
Embargoed file
Visibility date is undetermined

Dates and versions

pasteur-00583295 , version 1 (10-06-2011)

Identifiers

Cite

Neetu Gupta-Rossi, Odile Le Bail, Hedva Gonen, Christel Brou, Frédérique Logeat, et al.. Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor.. Journal of Biological Chemistry, 2001, 276 (37), pp.34371-8. ⟨10.1074/jbc.M101343200⟩. ⟨pasteur-00583295⟩

Collections

PASTEUR CNRS
103 View
2 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More