浙江大学生命科学研究院黄俊博士在2010年12月27日美国生化与分子生物学学会主办的JBC杂志在线发表研究论文“Angiomotin-like proteins associate with and negatively regulate YAP1”。该文是浙江大学生研院与美国M.D.安德森癌症中心合作的成果。M.D.安德森癌症中心王文奇博士是该文的第一作者，黄俊博士与Junjie Chen博士为该文的共同通讯作者。
hippo信号通路通过调节细胞增殖和细胞凋亡，行使着控制器官大小的重要功能。转录因子辅助因子YAP1（yes-associated protein 1）是这一信号通路中的一个关键蛋白。在本研究论文中，黄俊教授与Junjie Chen教授的研究小组合作克隆出了两个YAP1结合蛋白AMOTL1和AMOTL2，并发现它们通过影响YAP1的核质穿梭副调控YAP的功能。进一步的研究发现，在MCF10A细胞中降低AMOTL2的表达能够促进细胞发生上皮细胞向间充质细胞的转化（EMT），而这一表型恰好与YAP1在该细胞中过量表达的表型一致。
Angiomotin-like proteins associate with and negatively regulate YAP1
+ Author Affiliations
1 The University of Texas M. D. Anderson Cancer Center, United States;
2 Zhejiang University, China
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.
