Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis.
Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis.
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DOI：
10.1016/j.ydbio.2010.07.009
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发表时间：
2010-09-15
影响因子：
2.7
通讯作者：
Sugrue SP
中科院分区：
文献类型：
--
作者：
Joo JH;Taxter TJ;Munguba GC;Kim YH;Dhaduvai K;Dunn NW;Degan WJ;Oh SP;Sugrue SP
Pinin(PNN)是一种核斑点相关蛋白，已被证明通过改变几个关键黏附分子的表达而在维持上皮完整性方面发挥作用。在这里，我们证明了PNN通过影响肠道同源框基因CDX2的表达在小肠发育中发挥关键作用。肠上皮中PNN的条件性失活导致尾型同源框基因CDX2的显著下调，导致明显的绒毛畸形发育和严重的上皮分化中断。此外，在PNN缺陷的小肠中，我们观察到Tcf/LEF报告活性上调，以及β-连环蛋白和TCF4的错误表达/分布。由于CDx基因表达的调控与Wnt/β-catenin信号活性密切相关，我们探索了PNN与典型的Wnt信号通路的主要效应因子β-catenin相互作用的可能性。免疫共沉淀分析表明，PNN与其相互作用伙伴CtBP2(转录共抑制因子)与β-连环蛋白形成一个复合体。此外，这两种蛋白都被发现募集到CDX2的近端启动子区域。综上所述，我们的结果表明，PNN在小肠发育过程中对Wnt信号和CDX2表达的严格调控是必不可少的。
Pinin (Pnn), a nuclear speckle-associated protein, has been shown to function in maintenance of epithelial integrity through altering expression of several key adhesion molecules. Here we demonstrate that Pnn plays a crucial role in small intestinal development by influencing expression of an intestinal homeobox gene, Cdx2. Conditional inactivation of Pnn within intestinal epithelia resulted in significant downregulation of a caudal type homeobox gene, Cdx2, leading to obvious villus dysmorphogenesis and severely disrupted epithelial differentiation. Additionally, in Pnn-deficient small intestine, we observed upregulated Tcf/Lef reporter activity, as well as misregulated expression/distribution of β-catenin and Tcf4. Since regulation of Cdx gene expression has been closely linked to Wnt/β-catenin signaling activity, we explored the possibility of Pnn’s interaction with β-catenin, a major effector of the canonical Wnt signaling pathway. Co-immunoprecipitation assays revealed that Pnn, together with its interaction partner CtBP2, a transcriptional co-repressor, was in a complex with β-catenin. Moreover, both of these proteins were found to be recruited to the proximal promoter area of Cdx2. Taken together, our results suggest that Pnn is essential for tight regulation of Wnt signaling and Cdx2 expression during small intestinal development.
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影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
DOI：
10.1152/ajpgi.00037.2005
发表时间：
2005-08-01
影响因子：
4.5
作者：
Alkhoury, F;Malo, MS;Hodin, RA
通讯作者：
Hodin, RA
影响因子：
4.6
作者：
Andreu, P;Colnot, S;Romagnolo, B
通讯作者：
Romagnolo, B
DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
影响因子：
5.3
作者：
Alpatov, R;Munguba, GC;Sugrue, SP
通讯作者：
Sugrue, SP