Wackerhage Henning, Del Re Dominic P, Judson Robert N, Sudol Marius, Sadoshima Junichi
School of Medical Sciences, University of Aberdeen, Health Sciences Building, Foresterhill, AB25 2ZD Aberdeen, Scotland, UK.
Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, 185 South Orange Avenue, Newark, NJ 07103, USA.
Sci Signal. 2014 Aug 5;7(337):re4. doi: 10.1126/scisignal.2005096.
The discovery of the Hippo pathway can be traced back to two areas of research. Genetic screens in fruit flies led to the identification of the Hippo pathway kinases and scaffolding proteins that function together to suppress cell proliferation and tumor growth. Independent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads. Additionally, many other signal transduction proteins crosstalk to members of the Hippo pathway forming a Hippo signal transduction network. We discuss evidence that the Hippo signal transduction network plays important roles in myogenesis, regeneration, muscular dystrophy, and rhabdomyosarcoma in skeletal muscle, as well as in myogenesis, organ size control, and regeneration of the heart. Understanding the role of Hippo kinases in skeletal and heart muscle physiology could have important implications for translational research.
河马通路的发现可以追溯到两个研究领域。果蝇的基因筛选导致了河马通路激酶和支架蛋白的鉴定，它们共同作用以抑制细胞增殖和肿瘤生长。独立研究，通常是在肌肉生物学背景下，描述了Tead（TEA结构域）转录因子，其结合CATTCC DNA基序来调节基因表达。这两个研究领域因以下发现而联系起来：河马通路主要通过转录共激活因子Yap和Taz的磷酸化来调节Tead转录因子的活性，Yap和Taz与Tead结合并激活它们。此外，许多其他信号转导蛋白与河马通路的成员相互作用，形成一个河马信号转导网络。我们讨论了相关证据，表明河马信号转导网络在骨骼肌的肌生成、再生、肌肉营养不良和横纹肌肉瘤以及心脏的肌生成、器官大小控制和再生中发挥重要作用。了解河马激酶在骨骼肌和心肌生理学中的作用可能对转化研究具有重要意义。
