Crd-bp Mediates Stabilization of Betatrcp1 and C-myc Mrna in Response to Beta-catenin Signalling.
From: Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
Nature
- Publish Date: Jun 2006
- ISSN: 1476-4687
- Volume: 441
- Issue: 7095
- Pages: 898-901
- Medium: Internet
- Language: English
- Citation (JAMA): Noubissi Felicite K, Elcheva Irina, Bhatia Neehar, et al. Crd-bp Mediates Stabilization of Betatrcp1 and C-myc Mrna in Response to Beta-catenin Signalling.. Nature Jun 2006;441:898-901
Abstract
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.
Mesh Headings (Keywords): Animals, Cell Line, Genes, myc, Humans, I-kappa B Proteins, Mice, NF-kappa B, RNA Stability, RNA, Messenger, RNA-Binding Proteins, SKP Cullin F-Box Protein Ligases, Signal Transduction, TCF Transcription Factors, beta Catenin, beta-Transducin Repeat-Containing Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16778892
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