Essers Marieke A G, de Vries-Smits Lydia M M, Barker Nick, Polderman Paulien E, Burgering Boudewijn M T, Korswagen Hendrik C
Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, Netherlands.
Science. 2005 May 20;308(5725):1181-4. doi: 10.1126/science.1109083.
beta-Catenin is a multifunctional protein that mediates Wnt signaling by binding to members of the T cell factor (TCF) family of transcription factors. Here, we report an evolutionarily conserved interaction of beta-catenin with FOXO transcription factors, which are regulated by insulin and oxidative stress signaling. beta-Catenin binds directly to FOXO and enhances FOXO transcriptional activity in mammalian cells. In Caenorhabditis elegans, loss of the beta-catenin BAR-1 reduces the activity of the FOXO ortholog DAF-16 in dauer formation and life span. Association of beta-catenin with FOXO was enhanced in cells exposed to oxidative stress. Furthermore, BAR-1 was required for the oxidative stress-induced expression of the DAF-16 target gene sod-3 and for resistance to oxidative damage. These results demonstrate a role for beta-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress.
β-连环蛋白是一种多功能蛋白，它通过与转录因子T细胞因子（TCF）家族的成员结合来介导Wnt信号通路。在此，我们报道了β-连环蛋白与FOXO转录因子之间进化上保守的相互作用，FOXO转录因子受胰岛素和氧化应激信号调节。β-连环蛋白直接与FOXO结合，并增强其在哺乳动物细胞中的转录活性。在秀丽隐杆线虫中，β-连环蛋白BAR-1的缺失会降低FOXO直系同源物DAF-16在 dauer 形成和寿命方面的活性。在暴露于氧化应激的细胞中，β-连环蛋白与FOXO的关联增强。此外，BAR-1是氧化应激诱导的DAF-16靶基因sod-3表达以及抗氧化损伤所必需的。这些结果表明β-连环蛋白在调节FOXO功能中发挥作用，这在氧化应激条件下尤为重要。
