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NOS1AP Functionally Associates with YAP To Regulate Hippo Signaling

机译：NOS1AP在功能上与YAP关联以调节河马信号

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Deregulation of cellular polarity proteins and their associated complexes leads to changes in cell migration and proliferation. The nitric oxide synthase 1 adaptor protein (NOS1AP) associates with the tumor suppressor protein Scribble to control cell migration and oncogenic transformation. However, how NOS1AP is linked to the cell signaling events that curb oncogenic progression has remained elusive. Here we identify several novel NOS1AP isoforms, NOS1APd, NOS1APe, and NOS1APf, with distinct cellular localizations. We show that isoforms with a membrane-interacting phosphotyrosine binding (PTB) domain can associate with Scribble and recognize acidic phospholipids. In a screen to identify novel binding proteins, we have discovered a complex consisting of NOS1AP and the transcriptional coactivator YAP linking NOS1AP to the Hippo signaling pathway. Silencing of NOS1AP reduces the phosphorylation of YAP and of the upstream kinase Lats1. Conversely, expression of NOS1AP promotes YAP and Lats1 phosphorylation, which correlates with reduced TEAD activity and restricted cell proliferation. Together, these data implicate a role for NOS1AP in the regulation of core Hippo signaling and are consistent with the idea that NOS1AP functions as a tumor suppressor.
机译：细胞极性蛋白及其相关复合物的失调导致细胞迁移和增殖的变化。一氧化氮合酶1衔接蛋白（NOS1AP）与肿瘤抑制蛋白Scribble结合在一起，以控​​制细胞迁移和致癌转化。然而，如何将NOS1AP与抑制致癌性进展的细胞信号转导联系起来仍然难以捉摸。在这里，我们确定了几种新颖的NOS1AP亚型，NOS1APd，NOS1APe和NOS1APf，它们具有明显的细胞定位。我们显示具有与膜相互作用的磷酸酪氨酸结合（PTB）域的同工型可以与Scribble关联并识别酸性磷脂。在鉴定新型结合蛋白的筛选中，我们发现了由NOS1AP和将NOS1AP连接至Hippo信号通路的转录共激活因子YAP组成的复合物。沉默NOS1AP可减少YAP和上游激酶Lats1的磷酸化。相反，NOS1AP的表达促进YAP和Lats1磷酸化，这与降低的TEAD活性和细胞增殖受限有关。总之，这些数据暗示了NOS1AP在核心Hippo信号调节中的作用，并且与NOS1AP起到抑癌作用的想法相一致。

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