Department of Medical Biochemistry, Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
J Biochem. 2013 Sep;154(3):207-9. doi: 10.1093/jb/mvt060. Epub 2013 Jul 10.
The Hippo pathway was originally identified in Drosophila as the signalling pathway that governs organ size. The core of the pathway harbours two protein kinases (Hippo and Warts). Hippo phosphorylates and activates Warts, which in turn phosphorylates and inactivates the transcriptional co-activator Yorkie. As Yorkie mediates cell cycle-promoting and anti-apoptotic gene transcriptions, the Hippo pathway suppresses cell cycle progression and induces apoptosis. The pathway was named after Hippo, which was regarded as a key component. The pathway was initially considered to be well conserved in mammals. Indeed the mammalian homologues of Hippo, and Warts negatively regulate Yorkie homologue and function as the tumour suppressors. However, the researchers have identified numerous additional components both in Drosophila and mammals and the significant interspecies diversity is now evident. To make things more complicated, the regulation of the pathway does not necessarily depend on Hippo homologues. In this commentary, we reconsider what is essential for the Hippo pathway and try to sort out the controversial arguments in the discussion of the evolutionary root of the pathway.
Hippo 通路最初在果蝇中被确定为调节器官大小的信号通路。该通路的核心含有两个蛋白激酶(Hippo 和 Warts)。Hippo 磷酸化并激活 Warts,Warts 又磷酸化并失活转录共激活因子 Yorkie。由于 Yorkie 介导细胞周期促进和抗细胞凋亡基因转录,Hippo 通路抑制细胞周期进程并诱导细胞凋亡。该通路以 Hippo 命名,Hippo 被认为是关键组成部分。该通路最初被认为在哺乳动物中高度保守。事实上,Hippo 和 Warts 的哺乳动物同源物负调控 Yorkie 同源物,并作为肿瘤抑制因子发挥作用。然而,研究人员在果蝇和哺乳动物中都鉴定出了许多其他成分,物种间的显著多样性现在已经很明显。为了使事情更加复杂,该通路的调节不一定依赖于 Hippo 同源物。在这篇评论中,我们重新考虑 Hippo 通路的基本要素,并试图理清通路进化根源讨论中的争议论点。