CRD-BP mediates stabilization of βTrCP1 and c-myc mRNA in response to β-catenin signalling

Felicite K. Noubissi, Irina Elcheva, Neehar Bhatia, Abbas Shakoori, Andrei Ougolkov, Jianghuai Liu, Toshinari Minamoto, Jeff Ross, Serge Y. Fuchs, Vladimir S. Spiegelman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

Although constitutive activation of β-catenin/Tcf signalling is implicated in the development of human cancers, the mechanisms by which the β-catenin/Tcf pathway promotes tumorigenesis are incompletely understood. Messenger RNA turnover has a major function in regulating gene expression and is responsive to developmental and environmental signals. mRNA decay rates are dictated by cis-acting elements within the mRNA and by trans-acting factors, such as RNA-binding proteins (reviewed in refs 2, 3). Here we show that β-catenin stabilizes the mRNA encoding the F-box protein βTrCP1, and identify the RNA-binding protein CRD-BP (coding region determinant-binding protein) as a previously unknown target of β-catenin/Tcf transcription factor. CRD-BP binds to the coding region of βTrCP1 mRNA. Overexpression of CRD-BP stabilizes βTrCP1 mRNA and elevates βTrCP1 levels (both in cells and in vivo), resulting in the activation of the Skp1-Cullin1-F-box protein (SCF)βTrCP E3 ubiquitin ligase and in accelerated turnover of its substrates including IκB and β-catenin. CRD-BP is essential for the induction of both βTrCP1 and c-Myc by β-catenin signalling in colorectal cancer cells. High levels of CRD-BP that are found in primary human colorectal tumours exhibiting active β-catenin/Tcf signalling implicates CRD-BP induction in the upregulation of βTrCP1, in the activation of dimeric transcription factor NF-κB and in the suppression of apoptosis in these cancers.

Original languageEnglish (US)
Pages (from-to)898-901
Number of pages4
JournalNature
Volume441
Issue number7095
DOIs
StatePublished - Jun 15 2006

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'CRD-BP mediates stabilization of βTrCP1 and c-myc mRNA in response to β-catenin signalling'. Together they form a unique fingerprint.

Cite this