The TEAD/TEF family of transcription factor scalloped mediates hippo signaling in organ size control
The TEAD/TEF family of transcription factor scalloped mediates hippo signaling in organ size control
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DOI：
10.1016/j.devcel.2008.01.006
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发表时间：
2008-03-01
影响因子：
11.8
通讯作者：
Jiang, Jin
中科院分区：
文献类型：
--
作者：
Zhang, Lei;Ren, Fangfang;Jiang, Jin
Hippo （Hpo）信号通路通过控制执行这些过程的关键调控基因来控制细胞生长、增殖和凋亡；然而，该通路的转录因子仍然难以捉摸。本研究证明TEAD/TEF家族转录因子扇贝（Sd）与辅激活因子Yorkie （Yki）共同调控Hpo通路应答基因。Sd和Yki形成一个转录复合体，其活性受到Hpo信号的抑制。Sd过表达增强，而其失活抑制Yki过表达或Hpo通路肿瘤抑制基因突变引起的组织过度生长。Sd失活会降低Hpo靶基因的表达并减小器官大小，而组成活性Sd则会促进组织过度生长。Sd促进Yki的核定位，而Hpo信号通过磷酸化Yki的S168位点将Yki保留在细胞质中。最后，Sd将Yki招募到通路应答基因diap1的增强子上，表明diap1是Hpo通路的直接转录靶点。
The Hippo (Hpo) signaling pathway governs cell growth, proliferation, and apoptosis by controlling key regulatory genes that execute these processes; however, the transcription factor of the pathway has remained elusive. Here we provide evidence that the TEAD/TEF family transcription factor Scalloped (Sd) acts together with the coactivator Yorkie (Yki) to regulate Hpo pathway-responsive genes. Sd and Yki form a transcriptional complex whose activity is inhibited by Hpo signaling. Sd overexpression enhances, whereas its inactivation suppresses, tissue overgrowth caused by Yki overexpression or tumor suppressor mutations in the Hpo pathway. Inactivation of Sd diminishes Hpo target gene expression and reduces organ size, whereas a constitutively active Sd promotes tissue overgrowth. Sd promotes Yki nuclear localization, whereas Hpo signaling retains Yki in the cytoplasm by phosphorylating Yki at S168. Finally, Sd recruits Yki to the enhancer of the pathway-responsive gene diap1, suggesting that diap1 is a direct transcriptional target of the Hpo pathway.