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YAP转录共激活因子的调控与功能

The regulation and function of YAP transcription co-activator.

作者信息

Zhu Chu, Li Li, Zhao Bin

机构信息

Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou 310058, China.

Institute of Aging Research, Hangzhou Normal University, Hangzhou 311121, China

出版信息

Acta Biochim Biophys Sin (Shanghai). 2015 Jan;47(1):16-28. doi: 10.1093/abbs/gmu110. Epub 2014 Dec 8.

Abstract

The Hippo pathway was initially identified in Drosophila by genetic mosaic screens for tumor suppressor genes. Researches indicated that the Hippo pathway is a key regulator of organ size and is conserved during evolution. Furthermore, studies of mouse models and clinical samples demonstrated the importance of Hippo pathway dysregulation in human cancer development. In addition, the Hippo pathway contributes to progenitor cell and stem cell self-renewal and is thus involved in tissue regeneration. In the Hippo pathway, MST1/2 kinases together with the adaptor protein SAV phosphorylate LATS1/2 kinases. Interaction with an adaptor protein MOB is also important for LATS1/2 activation. Activated LATS1/2 in turn phosphorylate and inhibit Yes-associated protein (YAP). YAP is a key downstream effector of the Hippo pathway, and is a transcriptional co-activator that mainly interacts with TEAD family transcription factors to promote gene expression. Alteration of gene expression by YAP leads to cell proliferation, apoptosis evasion, and also stem cell amplification. In this review, we mainly focus on YAP, discussing its regulation and mechanisms of action in the context of organ size control, tissue regeneration and tumorigenesis.

摘要

河马通路最初是在果蝇中通过肿瘤抑制基因的遗传镶嵌筛选而被发现的。研究表明,河马通路是器官大小的关键调节因子,并且在进化过程中保守。此外,对小鼠模型和临床样本的研究证明了河马通路失调在人类癌症发展中的重要性。另外,河马通路有助于祖细胞和干细胞的自我更新,因此参与组织再生。在河马通路中,MST1/2激酶与衔接蛋白SAV一起磷酸化LATS1/2激酶。与衔接蛋白MOB的相互作用对于LATS1/2的激活也很重要。激活的LATS1/2进而磷酸化并抑制Yes相关蛋白(YAP)。YAP是河马通路的关键下游效应物,是一种转录共激活因子,主要与TEAD家族转录因子相互作用以促进基因表达。YAP引起的基因表达改变导致细胞增殖、逃避凋亡,还会导致干细胞扩增。在本综述中,我们主要聚焦于YAP,讨论其在器官大小控制、组织再生和肿瘤发生背景下的调节及其作用机制。

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