Ajuba LIM proteins are Snail/Slug corepressors required for neural crest development in Xenopus
Ajuba LIM proteins are Snail/Slug corepressors required for neural crest development in Xenopus
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DOI：
10.1016/j.devcel.2008.01.005
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发表时间：
2008-03-01
影响因子：
11.8
通讯作者：
Longmore, Gregory D.
中科院分区：
文献类型：
--
作者：
Langer, Ellen M.;Feng, Yunfeng;Longmore, Gregory D.
蜗牛家族转录抑制因子在生理和病理过程中调节上皮间质转化。所有脊椎动物 Snail 蛋白中都存在保守的 SNAG 抑制结构域，这是阻遏蛋白复合物组装所必需的。在这里，我们通过与 SNAG 结构域的相互作用将 LIM 蛋白的 Ajuba 家族鉴定为 Snail 家族的功能性辅阻遏物。 Ajuba LIM 蛋白与细胞核内源性 E-钙粘蛋白启动子上的 Snail 相互作用，并有助于 Snail 依赖性 E-钙粘蛋白抑制。使用爪蟾神经嵴作为体内 Snail 或 Slug 诱导的 EMT 模型，我们证明 Ajuba LIM 蛋白作为 Snail/Slug 辅抑制因子有助于神经嵴发育；并且是体内 Snail/Slug 功能所必需的。由于 Ajuba LIM 蛋白也是粘附连接的组成部分，并有助于其组装或稳定性，因此它们与细胞核中 Snail 蛋白的功能相互作用表明，Ajuba LIM 蛋白是上皮动态与核反应沟通表面事件的重要调节因子。
Snail family transcriptional repressors regulate epithelial mesenchymal transitions during physiological and pathological processes. A conserved SNAG repression domain present in all vertebrate Snail proteins is necessary for repressor complex assembly. Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. Ajuba LIM proteins interact with Snail in the nucleus on endogenous E-cadherin promoters and contribute to Snail-dependent repression of E-cadherin. Using Xenopus neural crest as a model of in vivo Snail- or Slug-induced EMT, we demonstrate that Ajuba LIM proteins contribute to neural crest development as Snail/Slug corepressors; and are required for in vivo Snail/Slug function. Because Ajuba LIM proteins are also components of adherens junctions and contribute to their assembly or stability, their functional interaction with Snail proteins in the nucleus suggests that Ajuba LIM proteins are important regulators of epithelia dynamics communicating surface events with nuclear responses.