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J. Biol. Chem., Vol. 280, Issue 9, 8581-8588, March 4, 2005

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Expression of axin2 Is Regulated by the Alternative 5'-Untranslated Regions of Its mRNA^*

Thomas A. Hughes and Hugh J. M. Brady

From the Molecular Haematology and Cancer Biology Unit, Camelia Botnar Laboratories, Institute of Child Health, 30 Guilford St., London WC1N 1EH, United Kingdom

Axin2 is a negative regulator of Wnt/-catenin signaling with roles in early development and tumor suppression. We find that axin2 expression is regulated at both transcriptional and translational levels. The gene allows transcription of mRNAs with three alternative 5'-untranslated regions, and these are differentially expressed in various human cell types. These untranslated regions can differentially determine protein expression from messages by influencing mRNA stability and translational efficiency. We identify short upstream reading frames and structural motifs that are responsible for modulation of mRNA translational efficiencies. We show that the proportions of axin2 message expressing each 5'-untranslated region influence the amount of Axin2 protein expressed within cells. We discuss this complex regulation in the context of the function of Axin2 as a tumor suppressor.

Received for publication, September 20, 2004 , and in revised form, December 9, 2004.

^* This work was supported by the Medical Research Council, UK. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 44-20-7242-9789 (ext. 2737); Fax: 44-20-7813-8100; E-mail: t.hughes{at}ich.ucl.ac.uk.

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