Intercollege Graduate Degree Program in Genetics, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Dev Biol. 2012 Sep 1;369(1):115-23. doi: 10.1016/j.ydbio.2012.06.014. Epub 2012 Jun 23.
Tissue growth is achieved through coordinated cellular growth, cell division and apoptosis. Hippo signaling is critical for monitoring tissue growth during animal development. Loss of Hippo signaling leads to tissue overgrowth due to continuous cell proliferation and block of apoptosis. As cells lacking Hippo signaling are similar in size compared to normal cells, cellular growth must be properly maintained in Hippo signaling-deficient cells. However, it is not clear how Hippo signaling might regulate cellular growth. Here we show that loss of Hippo signaling increased Akt (also called Protein Kinase B, PKB) expression and activity, whereas activation of Hippo signaling reduced Akt expression in developing tissues in Drosophila. While yorkie (yki) is sufficient to increase Akt expression, Akt up-regulation caused by the loss of Hippo signaling is strongly dependent on yki, indicating that Hippo signaling negatively regulates Akt expression through Yki inhibition. Consistently, genetic analysis revealed that Akt plays a critical role in facilitating growth of Hippo signaling-defective tissues. Thus, Hippo signaling not only blocks cell division and promotes apoptosis, but also regulates cellular growth by inhibiting the Akt pathway activity.
组织生长是通过细胞的协调生长、细胞分裂和细胞凋亡来实现的。 Hippo 信号通路对于动物发育过程中监测组织生长至关重要。 Hippo 信号通路的丧失会导致组织过度生长，这是由于细胞持续增殖和细胞凋亡受阻所致。由于缺乏 Hippo 信号通路的细胞与正常细胞的大小相似，因此必须在缺乏 Hippo 信号通路的细胞中适当维持细胞生长。然而，目前尚不清楚 Hippo 信号通路如何调节细胞生长。在这里，我们发现 Hippo 信号通路的丧失会增加 Akt（也称为蛋白激酶 B，PKB）的表达和活性，而 Hippo 信号通路的激活会减少果蝇发育组织中的 Akt 表达。虽然 yorkie（yki）足以增加 Akt 的表达，但由于 Hippo 信号通路的丧失导致的 Akt 上调强烈依赖于 yki，表明 Hippo 信号通路通过抑制 Yki 来负调控 Akt 的表达。一致地，遗传分析表明 Akt 在促进 Hippo 信号通路缺陷组织的生长中起着关键作用。因此，Hippo 信号通路不仅阻断细胞分裂并促进细胞凋亡，而且通过抑制 Akt 通路活性来调节细胞生长。
