The Wnt/β-catenin→Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs
The Wnt/β-catenin→Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs
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DOI：
10.1016/s1097-2765(03)00407-6
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发表时间：
2003-11-01
期刊：
影响因子：
16
通讯作者：
Gherzi, R
中科院分区：
文献类型：
--
作者：
Briata, P;Ilengo, C;Gherzi, R
Wnt/ β -catenin通路快速诱导细胞类型限制性转录因子Pitx2的转录，这是激活生长调节基因的有效细胞特异性增殖所必需的。在这里，我们报道了Pitx2 mRNA显示出快速的周转率，并且Wnt/ β -catenin通路的激活稳定了Pitx2 mRNA以及其他不稳定的mRNA，包括c-Jun， Cyclin D1和Cyclin D2，这些mRNA由同一通路的关键转录靶基因编码。我们的数据表明，Pitx2 mRNA的稳定是由于Pitx2 3'UTR与不稳定的富au元素（ARE）结合蛋白（bp） KSRP和TTP的相互作用减少，以及与稳定的ARE- bp HuR的相互作用增加。Pitx2本身是Wnt/ β -catenin诱导的mRNA稳定的介质。我们之前和现在的数据支持这样的假设，即单一途径可以协调调节序列转录和转录后事件，从而形成一个完整的功能基因调控网络。
The Wnt/beta-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/beta-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/beta-catenin-induced mRNA stabilization. Our previous and present data support the hypothesis that a single pathway can coordinately regulate sequential transcriptional and post-transcriptional events leading to an integrated functional gene regulatory network.