A C-elegans Myc-like network cooperates with semaphorin and Wnt signaling pathways to control cell migration
A C-elegans Myc-like network cooperates with semaphorin and Wnt signaling pathways to control cell migration
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DOI：
10.1016/j.ydbio.2007.07.034
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发表时间：
2007-10-15
影响因子：
2.7
通讯作者：
Ayer, Donald E.
中科院分区：
文献类型：
--
作者：
Pickett, Christopher L.;Breen, Kevin T.;Ayer, Donald E.
MYC和Mondo蛋白是细胞生长、增殖和能量代谢的关键调节因子，但经常被忽视的是它们在细胞迁移中的关键作用。蛋白质-蛋白质和蛋白质-DNA相互作用的复杂网络控制着Myc和Mondoa的转录活性，混淆了它们在高等真核生物中的功能分析。在这里，我们报告了一个简化的类Myc网络的转录激活臂在秀丽线虫中的鉴定。这个网络包括一个MLX同源基因，命名为MXL-2，代表Max-like 2，以及一个同时具有Mye和Mondo蛋白序列特征的蛋白质，命名为MML-1，代表Myc和Mondo-like 1。MML-1/MXL-2复合体在调节雄性尾部Ray I前体细胞的迁移方面具有主要功能。MML-1/MXL-2复合体控制非迁移性表皮中ECM成分的表达，我们认为这有助于邻近的射线1前体细胞迁移所需的底物。此外，我们还发现，促进迁移的Wnt/β-catenin和信号素信号通路与MML-1/MXL-2在遗传上相互作用，从而决定了Ray I的位置。对线虫Myc超家族的首次功能分析表明，Mondoa和Myc在细胞迁移中的作用可能比以前所认识的更重要，它们与其他促进迁移的途径的合作提供了对它们在细胞迁移中作用的更全面的看法。(C)2007 Elsevier Inc.保留所有权利。
Myc and Mondo proteins are key regulators of cell growth, proliferation, and energy metabolism, yet often overlooked is their vital role in cell migration. Complex networks of protein-protein and protein-DNA interactions control the transcriptional activity of Myc and MondoA confounding their functional analysis in higher eukaryotes. Here we report the identification of the transcriptional activation arm of a simplified Myc-like network in Caenorhabditis elegans. This network comprises an Mlx ortholog, named MXL-2 for Max-like 2, and a protein that has sequence features of both Mye and Mondo proteins, named MML-1 for Myc and Mondo-like 1. MML-1/MXL-2 complexes have a primary function in regulating migration of the ray I precursor cells in the male tail. MML-1/MXL-2 complexes control expression of ECM components in the non-migratory epidermis, which we propose contributes to the substratum required for migration of the neighboring ray 1 precursor cells. Furthermore, we show that pro-migratory Wnt/beta-catenin and semaphorin signaling pathways interact genetically with MML-1/MXL-2 to determine ray I position. This first functional analysis of the Myc superfamily in C elegans suggests that MondoA and Myc may have more predominant roles in cell migration than previously appreciated, and their cooperation with other pro-migratory pathways provides a more integrated view of their role in cell migration. (C) 2007 Elsevier Inc. All rights reserved.