the wnt/-catenin → pitx2 pathway controls the turnover of pitx2 and other unstable mrnas
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The Wnt/-Catenin → Pitx2 Pathway Controls the Turnover of Pitx2 and Other Unstable mRNAs. Molecular Cell, Vol. 12, 1201 – 1211, November, 2003. - PowerPoint PPT PresentationTRANSCRIPT
The Wnt/-Catenin→Pitx2 Pathway Controlsthe Turnover of Pitx2
and Other Unstable mRNAs
Molecular Cell, Vol. 12, 1201–1211, November, 2003.
Identification of a Wnt/Dvl/-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
Kioussi et al. Cell. 2002, 111(5):673-85
Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway.
Baek et al. Proc Natl Acad Sci U S A. 2003, 100(6):3245-50
From previous report
Rapid induction of Pitx2 by WntDuring development, tightly regulated expression of Pitx2 in time and space
It might exist additional mechanism that regulates Pitx2 expression as well as TCF/LEF dependent manner
Regulation of gene expression Transcriptional regulation Regulation of RNA stability
Rapid mRNA degradation requires three components
Figure.1
Instability elements: ARETrans-acting factors: ARE-BPsEnzyme: exosome
Altogether these data suggest that
The expression of Pitx2 can be regulated at the level of its transcript turnover.
Two regions, the CDS and the 3′UTR, contain destabilizing sequences.
Pitx2 3′UTR displays class III ARE mediating exosome-dependent mRNA degradation
Figure.2
Altogether our findings suggest that
the molecular target of Wnt signaling isthe ARE-mediated decay of the mRNA.
Wnt signaling regulates both transcriptional and mRNA turnover changes.
Figure.3A. Specific interaction of ARE-BPs with Pitx2 3`-UTR in vitro.
Changes in ARE-BPs interacted with Pitx2 RNA by Wnt signaling
Wnt signaling induces changes in the nucleocytoplasmic distribution of ARE-BPs
Figure.5
Pitx2 plays a central role in the Wnt-activated regulatory pathway that stabilizes Pitx2, Cyclin D1, Cyclin D2, and c-Jun RNAs.
Wnt
-catenin
LEF/TCF
Pitx2C-Jun Cyclin D1
CyclinD2
ARE-BPs subcellular localization
TTP-AREKSRP-AREHuR-ARE
mRNA stabilization