The TEAD/TEF family protein scalloped mediates transcriptional output of the hippo growth-regulatory pathway
The TEAD/TEF family protein scalloped mediates transcriptional output of the hippo growth-regulatory pathway
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DOI：
10.1016/j.devcel.2008.01.007
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发表时间：
2008-03-01
影响因子：
11.8
通讯作者：
Pan, Duojia
中科院分区：
文献类型：
--
作者：
Wu, Shian;Liu, Yi;Pan, Duojia
Hippo（Hpo）激酶级联通过使转录共激活因子Yorkie（Yki）失活来限制组织生长，所述转录共激活因子Yorkie（Yki）通过未知机制调节靶基因（例如细胞死亡抑制剂diap 1）的表达。在这里，我们确定了TEAD/TEF家族蛋白扇贝（Sd）作为一个DNA结合转录因子，与Yki的合作伙伴介导的转录输出的Hpo生长调节途径。diap 1（th）位点具有最小的Sd结合Hpo应答元件（HRE），其介导Hpo途径的转录调节。Sd直接与Yki结合，并且消除Sd-Yki结合的Yki错义突变也使体内Yki功能失活。我们进一步证明sd是yki诱导的组织过度生长和靶基因表达所必需的，并且sd活性在其哺乳动物同源物中是保守的。我们的研究结果揭示了迄今为止在Hpo信号通路中缺失的一个环节，并提供了一个Hpo响应增强子元件上的分子事件的一瞥。
The Hippo (Hpo) kinase cascade restricts tissue growth by inactivating the transcriptional coactivator Yorkie (Yki), which regulates the expression of target genes such as the cell death inhibitor diap1 by unknown mechanisms. Here we identify the TEAD/TEF family protein Scalloped (Sd) as a DNA-binding transcription factor that partners with Yki to mediate the transcriptional output of the Hpo growth-regulatory pathway. The diap1 (th) locus harbors a minimal Sd-binding Hpo Responsive Element (HRE) that mediates transcriptional regulation by the Hpo pathway. Sd binds directly to Yki, and a Yki missense mutation that abrogates Sd-Yki binding also inactivates Yki function in vivo. We further demonstrate that sd is required for yki-induced tissue overgrowth and target gene expression, and that sd activity is conserved in its mammalian homolog. Our results uncover a heretofore missing link in the Hpo signaling pathway and provide a glimpse of the molecular events on a Hpo-responsive enhancer element.