Mask is required for the activity of the Hippo pathway effector Yki/YAP.
Mask is required for the activity of the Hippo pathway effector Yki/YAP.
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DOI：
10.1016/j.cub.2012.12.033
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发表时间：
2013-02-04
期刊：
影响因子：
9.2
通讯作者：
Halder, Georg
中科院分区：
文献类型：
--
作者：
Sansores-Garcia, Leticia;Atkins, Mardelle;Moya, Ivan M.;Shahmoradgoli, Maria;Tao, Chunyao;Mills, Gordon B.;Halder, Georg
果蝇Yorkie （Yki）蛋白及其在哺乳动物中的同源物Yes-associated protein （YAP）是有效的生长促进剂，YAP过表达与多种类型的癌症有关。Yki和YAP是转录共激活因子，是Hippo肿瘤抑制通路的下游效应物。Hippo信号通路对Yki和YAP的调控已被广泛研究，然而，它们如何调控基因表达却知之甚少。为了确定Yki活性的其他调节因子，我们在果蝇S2细胞中进行了全基因组RNAi筛选。在这个筛选中，我们在体外鉴定出保守蛋白Mask （Multiple ankyrin repeats single KH domain）作为一种新的Yki活性启动子，并在果蝇体内验证了这种功能。我们发现，Yki在Hippo通路下游需要Mask来诱导靶基因表达，并且Mask与Yki形成复合物。人类面罩同源物MASK1与YAP复合物，它是YAP充分活性所必需的，MASK1表达升高与乳腺癌患者预后恶化相关。我们得出结论，在发育和肿瘤发生过程中，Mask是一种新的Yki/YAP辅助因子，是最佳Yki/YAP活性所必需的。
The Drosophila Yorkie (Yki) protein and its mammalian homolog Yes-associated protein (YAP) are potent growth promoters and YAP overexpression is associated with multiple types of cancer. Yki and YAP are transcriptional co-activators and function as downstream effectors of the Hippo tumor suppressor pathway. The regulation of Yki and YAP by the Hippo signaling pathway has been extensively investigated, however, how they regulate gene expression is poorly understood. To identify additional regulators of Yki activity we performed a genome-wide RNAi screen in Drosophila S2 cells. In this screen, we identified the conserved protein Mask (Multiple ankyrin repeats single KH domain) as a novel promoter of Yki activity in vitro and validated this function in vivo in Drosophila. We found that Mask is required downstream of the Hippo pathway for Yki to induce target gene expression and that Mask forms complexes with Yki. The human Mask homolog MASK1 complexes with YAP and it is required for full activity of YAP and elevated MASK1 expression is associated with worsened outcomes for breast cancer patients. We conclude that Mask is a novel cofactor for Yki/YAP required for optimal Yki/YAP activity during development and oncogenesis.
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影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
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DOI：
10.1016/j.bbadis.2006.07.010
发表时间：
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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