Kodaka Manami, Hata Yutaka
Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
Cell Mol Life Sci. 2015 Jan;72(2):285-306. doi: 10.1007/s00018-014-1742-9. Epub 2014 Sep 30.
The Hippo pathway was originally identified as the signaling that controls organ size in Drosophila, with the core architecture conserved in mammals. In the mammalian Hippo pathway, mammalian Ste20-like kinases (MST1/2) and large tumor suppressor kinases (LATS1/2) regulate transcriptional co-activators, Yes-associated protein (YAP1) and Transcriptional co-activator with a PDZ-binding motif (TAZ). The Hippo pathway was initially thought to be quite straightforward; however, the identification of additional components has revealed its inherent complexity. Regulation of YAP1 and TAZ is not always dependent on MST1/2 and LATS1/2. MST1/2 and LATS1/2 play various YAP1/TAZ-independent roles, while YAP1 and TAZ cross-talk with other signaling pathways. In this review we focus on YAP1 and TAZ and discuss their regulation, function, and the consequences of their dysregulation.
Hippo信号通路最初被确定为控制果蝇器官大小的信号传导途径,其核心结构在哺乳动物中保守。在哺乳动物的Hippo信号通路中,哺乳动物Ste20样激酶(MST1/2)和大肿瘤抑制激酶(LATS1/2)调节转录共激活因子Yes相关蛋白(YAP1)和具有PDZ结合基序的转录共激活因子(TAZ)。Hippo信号通路最初被认为相当简单;然而,其他成分的发现揭示了其内在的复杂性。YAP1和TAZ的调节并不总是依赖于MST1/2和LATS1/2。MST1/2和LATS1/2发挥各种不依赖于YAP1/TAZ的作用,而YAP1和TAZ与其他信号通路相互作用。在这篇综述中,我们聚焦于YAP1和TAZ,并讨论它们的调节、功能以及失调的后果。