8月6日，国际知名学术期刊《PLoS Biology》在线发表了中科院上海生科院生化与细胞所张雷研究组、刘新垣研究组和赵允研究组合作完成的最新研究成果——“Par-1 regulates tissue growth by influencing hippo phosphorylate on status and hippo-salvador association”。在这项工作中，博士研究生黄宏龄等人发现了一个新的Hippo信号通路成员Par-1激酶，阐明了其在Hippo信号通路中负调控Hippo激酶活性的作用机制，并初步揭示了这种调控机制的保守性。
Hippo信号通路控制了脊椎动物以及非脊椎动物众多发育过程中细胞的生长及器官的大小，其异常将会导致包括发育缺陷及肿瘤、癌症在内的多种发育异常和生理性疾病。在果蝇中，Hippo通路上游的信号经过一系列激酶复合物的磷酸化级联反应，最终通过磷酸化下游的效应因子Yorkie，使其滞留在胞质内，不能进入细胞核行使其转录激活功能，从而实现对组织的生长调控。黄宏龄等人通过一系列遗传、分子和细胞生物学研究手段发现，Par-1与Hippo和支架蛋白Salvador相互作用，并证实Par-1能通过调节Hippo Ser30位点磷酸化及 Hippo-Salvador复合物的稳定性，从而负调节Hippo信号通路。
由于Hippo通路在进化上是最为保守的信号通路之一，果蝇中Hippo信号转导机制的研究对深入理解哺乳动物中Hippo信号途径的作用机制及其缺陷导致的相关癌症的靶向治疗具有十分重要的借鉴意义。
黄宏龄与王诗敏为本文的共同第一作者，该项工作得到了浙江大学赵斌教授课题组的大力支持，并获得了国家科技部、国家基金委以及中国科学院（干细胞先导专项）的资助。（生物谷Bioon.com）
doi:10.1371/journal.pbio.1001620
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Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association
Huang H-L, Wang S, Yin M-X, Dong L, Wang C, et al
The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network.
