浙江大學(xué)生命科學(xué)研究院黃俊博士在2010年12月27日美國(guó)生化與分子生物學(xué)學(xué)會(huì)主辦的JBC雜志在線(xiàn)發(fā)表研究論文“Angiomotin-like proteins associate with and negatively regulate YAP1”,。該文是浙江大學(xué)生研院與美國(guó)M.D.安德森癌癥中心合作的成果。M.D.安德森癌癥中心王文奇博士是該文的第一作者,，黃俊博士與Junjie Chen博士為該文的共同通訊作者,。
hippo信號(hào)通路通過(guò)調(diào)節(jié)細(xì)胞增殖和細(xì)胞凋亡，行使著控制器官大小的重要功能,。轉(zhuǎn)錄因子輔助因子YAP1（yes-associated protein 1）是這一信號(hào)通路中的一個(gè)關(guān)鍵蛋白,。在本研究論文中，黃俊教授與Junjie Chen教授的研究小組合作克隆出了兩個(gè)YAP1結(jié)合蛋白AMOTL1和AMOTL2,，并發(fā)現(xiàn)它們通過(guò)影響YAP1的核質(zhì)穿梭副調(diào)控YAP的功能,。進(jìn)一步的研究發(fā)現(xiàn)，在MCF10A細(xì)胞中降低AMOTL2的表達(dá)能夠促進(jìn)細(xì)胞發(fā)生上皮細(xì)胞向間充質(zhì)細(xì)胞的轉(zhuǎn)化（EMT）,，而這一表型恰好與YAP1在該細(xì)胞中過(guò)量表達(dá)的表型一致,。（生物谷Bioon.com）
生物谷推薦原文出處：
The Journal of Biological Chemistry doi: 10.1074/jbc.C110.205401
Angiomotin-like proteins associate with and negatively regulate YAP1
Wenqi Wang1, Jun Huang2 and Junjie Chen1,*
Abstract
In both Drosophila and mammalian systems, the hippo pathway plays an important role in controlling organ size, mainly through its ability to regulate cell proliferation and apoptosis. The key component in hippo pathway is the yes-associated protein YAP1, which localizes in nucleus, functions as a transcriptional coactivator and regulates the expression of several proliferation and apoptosis related genes. Hippo pathway negatively regulates YAP1 transcriptional activity by modulating its nuclear-cytoplasmic localization in a phosphorylation-dependent manner. Here we describe the identification of several new PY motif-containing proteins, including angiomotin like protein 1 (AMOTL1) and 2 (AMOTL2), as YAP1-associated proteins. We demonstrate that AMOTL1 and AMOTL2 can regulate YAP1 cytoplasm-to-nucleus translocation through direct protein-protein interaction, which can occur independent of YAP1 phosphorylation status. Moreover, downregulation of AMOTL2 in MCF10A cells promotes epithelial-mesenchymal transition (EMT), a phenotype that is also observed in MCF10A cells with YAP1 overexpression. Together, these data support a new mechanism for YAP1 regulation, which is mediated via its direct interactions with angiomotin like proteins.
