美國加州大學圣地亞哥分校管坤良教授研究小組最新發(fā)現(xiàn)Hippo-YAP通路是聯(lián)系器官大小調節(jié)與癌癥的分子信號通路系統(tǒng),。
Hippo信號轉導通路是幾年前發(fā)現(xiàn)的一個信號轉導通路,。研究發(fā)現(xiàn)Hippo信號通路是參與調控器官大小發(fā)育的關鍵信號通路，這一觀點首先在果蠅中被發(fā)現(xiàn),，后來的研究發(fā)現(xiàn)在哺乳動物的發(fā)育過程中Hippo有相同的功能,。06年Cell發(fā)表的一篇文章證實Hippo是一種細胞分裂和死亡的控制開關。Hippo信號轉導通路通過促進細胞調亡和限制細胞增殖調控器官大小的發(fā)育,，越來越多的證據(jù)表明,，Hippo信號的調控可能與人類的腫瘤發(fā)生密切相關。
最新研究發(fā)現(xiàn),，在Hippo的下游存在一種轉錄激活子Yki/YAP/TAZ,。在哺乳動物細胞中，Hippo pathway kinase cascade（Hippo通路級聯(lián)激酶）通過磷酸化和促進細胞質轉位來抑制YAP及其同系物TAZ的功能,。TEAD家族轉錄因子是進化上保守的影響YAP生物功能的關鍵因子,。
Yap是一個候選的致癌基因，而Hippo通路上的其他幾個因子是腫瘤抑制因子,。如果Hippo通路功能失調將導致癌細胞喪失接觸性抑制（癌細胞不受接觸性抑制局限將更容易擴散,，腫瘤灶將更快地擴散）。
因此,，Hippo-YAP通路是控制器官大小發(fā)育與腫瘤發(fā)生的一個信號轉導通路,。（生物谷Bioon.com）
生物谷專訪管坤良教授
生物谷推薦原始出處：
Current Opinion in Cell Biology Volume 20, Issue 6, December 2008,doi:10.1016/j.ceb.2008.10.001
The Hippo–YAP pathway: new connections between regulation of organ size and cancer
Bin Zhao1, 2, Qun-Ying Lei3, and Kun-Liang Guan1,
1Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093-0815, USA
2Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
3Department of Biological Chemistry, School of Medicine, and Molecular and Cellular Biology Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
The control of organ size is a basic biological question. In the past several years, the Hippo signaling pathway has been delineated and shown to be crucial in control of organ size in both Drosophila and mammals. Acting downstream of the Hippo pathway is the Yki/YAP/TAZ transcription co-activators. In mammalian cells, the Hippo pathway kinase cascade inhibits YAP and its paralog TAZ by phosphorylation and promotion of their cytoplasmic localization. The TEAD family transcription factors have recently been identified as evolutionarily conserved key mediators of YAP biological functions. yap is a candidate oncogene, and several other components of the Hippo pathway are tumor suppressors. Dysregulation of the Hippo pathway contributes to the loss of contact inhibition observed in cancer cells. Therefore, the Hippo–YAP pathway connects the regulation of organ size and tumorigenesis.
