The Wnt/β-catenin→Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs

Paola Briata, Cristina Ilengo, Giorgio Corte, Christoph Moroni, Michael G. Rosenfeld, Ching Yi Chen, Roberto Gherzi

Research output: Contribution to journalArticle

Abstract

The Wnt/β-catenin pathway rapidly induces the transcription of the cell-type-restricted transcription factor Pitx2 that is required for effective cell-specific proliferation activating growth-regulating genes. Here we report that Pitx2 mRNA displays a rapid turnover rate and that activation of the Wnt/β-catenin pathway stabilizes Pitx2 mRNA as well as other unstable mRNAs, including c-Jun, Cyclin D1, and Cyclin D2, encoded by critical transcriptional target genes of the same pathway. Our data indicate that Pitx2 mRNA stabilization is due to a reduced interaction of Pitx2 3′UTR with the destabilizing AU-rich element (ARE) binding proteins (BPs) KSRP and TTP as well as to an increased interaction with a stabilizing ARE-BP, HuR. Pitx2 itself is a mediator of Wnt/β-catenin-induced mRNA stabilization. Our previous and present data support the hypothesis that a single pathway can coordinately regulate sequential transcriptional and posttranscriptional events leading to an integrated functional gene regulatory network.

Original languageEnglish
Pages (from-to)1201-1211
Number of pages11
JournalMolecular Cell
Volume12
Issue number5
DOIs
Publication statusPublished - Nov 2003

ASJC Scopus subject areas

  • Molecular Biology

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