Notch post-translationally regulates β-catenin protein in stem and progenitor cells

Chulan Kwon, Paul Cheng, Isabelle N. King, Peter Andersen, Lincoln Shenje, Vishal Nigam, Deepak Srivastava

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

Cellular decisions of self-renewal or differentiation arise from integration and reciprocal titration of numerous regulatory networks. Notch and Wnt/β-catenin signalling often intersect in stem and progenitor cells and regulate each other transcriptionally. The biological outcome of signalling through each pathway often depends on the context and timing as cells progress through stages of differentiation. Here, we show that membrane-bound Notch physically associates with unphosphorylated (active) β-catenin in stem and colon cancer cells and negatively regulates post-translational accumulation of active β-catenin protein. Notch-dependent regulation of β-catenin protein did not require ligand-dependent membrane cleavage of Notch or the glycogen synthase kinase-3β-dependent activity of the β-catenin destruction complex. It did, however, require the endocytic adaptor protein Numb and lysosomal activity. This study reveals a previously unrecognized function of Notch in negatively titrating active β-catenin protein levels in stem and progenitor cells.

Original languageEnglish (US)
Pages (from-to)1244-1251
Number of pages8
JournalNature Cell Biology
Volume13
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kwon, C., Cheng, P., King, I. N., Andersen, P., Shenje, L., Nigam, V., & Srivastava, D. (2011). Notch post-translationally regulates β-catenin protein in stem and progenitor cells. Nature Cell Biology, 13(10), 1244-1251. https://doi.org/10.1038/ncb2313