Wnt/β-catenin signaling induces the expression and activity of βTrCP ubiquitin ligase receptor

Vladimir S. Spiegelman, Thomas J. Slaga, Michele Pagano, Toshinari Minamoto, Ze'ev Ronai, Serge Y. Fuchs

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

β-Transducing repeat-containing protein (βTrCP) targets the ubiquitination and subsequent degradation of both β-catenin and IκB, thereby playing an important role in β-catenin/Tcf and NF-κB-dependent signaling. Here evidence is presented that β-catenin/Tcf signaling elevates the expression of βTrCP mRNA and protein in a Tcf-dependent manner, which does not require βTrCP transcription. Induction of βTrCP expression by the β-catenin/Tcf pathway results in an accelerated degradation of the wild-type β-catenin, suggesting that the negative feedback loop regulation may control the β-catenin/Tcf pathway. This signaling also upregulated NF-κB transactivation without affecting the activity of IκB kinase, thereby establishing that the maintenance of the βTrCP level is important for coordination between β-catenin/Tcf and NF-κB signaling.

Original languageEnglish (US)
Pages (from-to)877-882
Number of pages6
JournalMolecular cell
Volume5
Issue number5
DOIs
Publication statusPublished - Jan 1 2000

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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