Kidd Ambrose R, Miskowski Jennifer A, Siegfried Kellee R, Sawa Hitoshi, Kimble Judith
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Wisconsin 53706, USA.
Cell. 2005 Jun 3;121(5):761-72. doi: 10.1016/j.cell.2005.03.029.
Wnt/MAPK signaling is a common variant of Wnt signaling in C. elegans and has been implicated in vertebrates. The sys-1 gene works with Wnt/MAPK signaling to control cell fates during C. elegans development. We report that the SYS-1 amino acid sequence is novel but that SYS-1 functions as beta-catenin: SYS-1 rescues a bar-1/beta-catenin null mutant, binds the POP-1/TCF beta-catenin binding domain, and coactivates POP-1-dependent transcription. Moreover, we provide genetic and molecular evidence that SYS-1 levels are crucial to POP-1 activity. Our results suggest that Wnt/MAPK signaling promotes POP-1 export from the nucleus to accommodate the limiting availability of its SYS-1/beta-catenin transcriptional coactivator. Discovery of SYS-1/beta-catenin extends our definition of beta-catenins and brings together aspects of the canonical mechanism for Wnt signaling with the noncanonical Wnt/MAPK mechanism. We discuss the idea that a similar pathway may be employed broadly in animal development.
Wnt/MAPK信号通路是秀丽隐杆线虫中Wnt信号通路的一种常见变体，在脊椎动物中也有涉及。sys-1基因与Wnt/MAPK信号通路共同作用，在秀丽隐杆线虫发育过程中控制细胞命运。我们报告称，SYS-1的氨基酸序列是全新的，但SYS-1发挥着β-连环蛋白的功能：SYS-1拯救了bar-1/β-连环蛋白缺失突变体，与POP-1/TCFβ-连环蛋白结合域结合，并共同激活依赖POP-1的转录。此外，我们提供了遗传和分子证据，表明SYS-1水平对POP-1活性至关重要。我们的结果表明，Wnt/MAPK信号通路促进POP-1从细胞核输出，以适应其SYS-1/β-连环蛋白转录共激活因子的有限可用性。SYS-1/β-连环蛋白的发现扩展了我们对β-连环蛋白的定义，并将Wnt信号通路的经典机制与非经典Wnt/MAPK机制的各个方面结合在一起。我们讨论了这样一种观点，即类似的通路可能在动物发育中广泛应用。
