High levels of Notch signaling down-regulate Numb and Numblike

Gavin Chapman, Lining Liu, Cecilia Sahlgren, Camilla Dahlqvist, Urban Lendahl*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

66 Citations (Scopus)

Abstract

Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in cultured cells and in the developing chick central nervous system. The Notch intracellular domain but not the canonical Notch downstream proteins Hes 1 and Hey 1 caused a reduction of Numb and Numblike. The Notch-mediated reduction of Numblike required the PEST domain in the Numblike protein and was blocked by the proteasome inhibitor MG132. Collectively, these observations reveal a reciprocal negative regulation between Notch and Numb/Numblike, which may be of relevance for stabilizing asymmetric cell fate switches and for tumor development.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalJournal of Cell Biology
Volume175
Issue number4
DOIs
Publication statusPublished - 20 Nov 2006
Externally publishedYes
MoE publication typeA1 Journal article-refereed

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