An NF-kappaB and slug regulatory loop active in early vertebrate mesoderm.
An NF-kappaB and slug regulatory loop active in early vertebrate mesoderm.
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DOI：
10.1371/journal.pone.0000106
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发表时间：
2006-12-27
期刊：
影响因子：
3.7
通讯作者：
Klymkowsky, Michael W.
中科院分区：
文献类型：
--
作者：
Zhang, Chi;Carl, Timothy F.;Trudeau, Evan D.;Simmet, Thomas;Klymkowsky, Michael W.
在果蝇和小鼠中，锌指转录因子Snail是中胚层形成所必需的;其脊椎动物寄生虫Slug（Snai2）似乎是小鸡和爪蛙非洲爪蟾神经嵴形成所必需的。Slug和Snail都可以诱导上皮细胞向间质细胞转化（EMT）并抑制细胞凋亡。基于吗啉代的功能丧失研究表明，Slug是X中中胚层和神经嵴标志物正常表达所必需的。光滑。这两种表型都可以通过注射编码抗凋亡蛋白Bcl-xL的RNA来挽救; Bcl-xL的作用依赖于I κ B激酶介导的双组分转录因子NF-κ B的活化。NF-κ B反过来直接上调Slug和Snail RNA的水平。Slug间接上调编码NF-κ B亚基蛋白RelA、Rel2和Rel3的RNA水平，并直接下调促凋亡Caspase-9 RNA水平。这些研究揭示了Slug/Snail-NF-κ B调节回路，类似于早期果蝇胚胎中存在的回路，在非洲爪蟾中胚层形成期间活跃。这是一种在炎症和转移性疾病的发展和过程中都具有重要意义的调节相互作用。
In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IκB kinase-mediated activation of the bipartite transcription factor NF-κB. NF-κB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-κB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. These studies reveal a Slug/Snail–NF-κB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease.
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影响因子：
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