Kikuchi Akira, Kishida Shosei, Yamamoto Hideki
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Exp Mol Med. 2006 Feb 28;38(1):1-10. doi: 10.1038/emm.2006.1.
The Wnt signaling pathway is conserved in various species from worms to mammals, and plays important roles in cellular proliferation, differentiation, and migration. Wnt stabilizes cytoplasmic beta-catenin and then the accumulated beta-catenin is translocated into the nucleus, where it activates the transcriptional factor T-cell factor (Tcf)/lymphoid enhancer factor (Lef), and thereby stimulates the expression of genes including c-myc, c-jun, fra-1, and cyclin D1. Tight regulation of this response involves post-translational modifications of the components of the Wnt signaling pathway. Phosphorylation, ubiquitination, and sumoylation have been shown to affect the half-life of beta-catenin and the transcriptional activity of Tcf/Lef. The precise spatio-temporal patterns of these multiple modifications determine the driving force of various cellular responses.
Wnt信号通路在从蠕虫到哺乳动物的各种物种中都是保守的，并且在细胞增殖、分化和迁移中发挥重要作用。Wnt使细胞质中的β-连环蛋白稳定，然后积累的β-连环蛋白被转运到细胞核中，在那里它激活转录因子T细胞因子（Tcf）/淋巴增强因子（Lef），从而刺激包括c-myc、c-jun、fra-1和细胞周期蛋白D1在内的基因表达。对这种反应的严格调控涉及Wnt信号通路成分的翻译后修饰。磷酸化、泛素化和类泛素化已被证明会影响β-连环蛋白的半衰期以及Tcf/Lef的转录活性。这些多种修饰的精确时空模式决定了各种细胞反应的驱动力。
