摘要
Hippo通路是一种在进化中形成的保守的蛋白激酶级联通路,它与发育中器官的大小和肿瘤的形成有关。Hippo通路的中枢是从肿瘤抑制子Hippo到原癌蛋白YAP/TAZ的激酶级联反应。YAP/TAZ是Hippo通路下游的主要的效应分子,它们广泛表达于多种组织器官中。在哺乳动物细胞中,Hippo通路激酶级联反应通过对YAP/TAZ磷酸化作用,促使其从细胞核转入细胞质中,从而抑制了YAP/TAZ的功能作用。TEAD家族转录子被鉴定为YAP/TAZ发挥生物学功能的重要调节因子。YAP/TAZ的失调引起的相关的基因的表达改变,将会影响细胞的增殖,分化,以及凋亡,从而会影响器官的大小以及肿瘤的形成。本文综述Hippo通路的最新进展,重点关注的是该通路中的YAP/TAZ调控的缺失对发育缺陷和肿瘤的影响。这将为我们研究再生医学,组织工程技术,肿瘤的干预防治提供新的思路与策略。
The Hippo pathway is an evolutionally conserved protein kinase cascade involved in both organ size control and tumorigenesis. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo to the oncoprotein YAP/TAZ. YAP/TAZ are the major downstream effectors of the Hippo pathway YAP/TAZ are expressed in a wide range of tissues. In mammalian celis, the Hippo pathway kinase cascade inhibits YAP/TAZ by phosphorylation and promotion of their cytoplasmic localization. The TEAD family transcription factors have been identified as key mediators of YAP/TAZ biological functions. Altered gene expression resulting from YAP/TAZ deregulation affects cell proliferation, differentiation and apoptosis, thereby affecting organ size and tumorigenesis. Here we review recent progresses of Hippo pathway by focusing on how loss of regulation of YAP/TAZ results in defects of development and cancers. It can provide the new ideas and strategies for us to study regenerative medicine, tissue engineering technology, the intervention of the tumor.
出处
《现代生物医学进展》
CAS
2013年第2期379-381,302,共4页
Progress in Modern Biomedicine
