Although constitutive activation of beta-catenin/Tcf signalling is implicated in 
the development of human cancers, the mechanisms by which the beta-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 beta-catenin 
stabilizes the mRNA encoding the F-box protein betaTrCP1, and identify the 
RNA-binding protein CRD-BP (coding region determinant-binding protein) as a 
previously unknown target of beta-catenin/Tcf transcription factor. CRD-BP binds 
to the coding region of betaTrCP1 mRNA. Overexpression of CRD-BP stabilizes 
betaTrCP1 mRNA and elevates betaTrCP1 levels (both in cells and in vivo), 
resulting in the activation of the Skp1-Cullin1-F-box protein (SCF)(betaTrCP) E3 
ubiquitin ligase and in accelerated turnover of its substrates including IkappaB 
and beta-catenin. CRD-BP is essential for the induction of both betaTrCP1 and 
c-Myc by beta-catenin signalling in colorectal cancer cells. High levels of 
CRD-BP that are found in primary human colorectal tumours exhibiting active 
beta-catenin/Tcf signalling implicates CRD-BP induction in the upregulation of 
betaTrCP1, in the activation of dimeric transcription factor NF-kappaB and in 
the suppression of apoptosis in these cancers.