Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap.
Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap.
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DOI：
10.1016/j.devcel.2010.09.009
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发表时间：
2010-10-19
影响因子：
11.8
通讯作者：
Johnston, Laura A.
中科院分区：
文献类型：
--
作者：
Neto-Silva, Ricardo M.;de Beco, Simon;Johnston, Laura A.
了解如何控制动物体型需要了解正负生长调节信号如何在细胞内平衡和整合。在这里，我们证明保守的生长促进转录因子 Myc 和肿瘤抑制 Hippo 通路的活性在果蝇成虫盘的生长过程中是相互依赖的。我们发现，Hippo 通路转导子 Yap 的果蝇同源物 Yorkie (Yki) 调节 Myc 的转录，并且 Myc 作为该通路的关键细胞生长效应器发挥作用。我们证明，反过来，Myc 作为其自身细胞水平的函数来调节 Yki 的表达，因此高水平的 Myc 通过转录和转录后机制抑制 Yki 的表达。我们提出，相互依赖的调节关系在功能上协调 Yki 和 Myc 的细胞活动，并提供一种调节器官大小的生长控制机制，并对癌症具有广泛的影响。
An understanding of how animal size is controlled requires knowledge of how positive and negative growth regulatory signals are balanced and integrated within cells. Here we demonstrate that the activities of the conserved growth promoting transcription factor Myc and the tumor-suppressing Hippo pathway are co-dependent during growth of Drosophila imaginal discs. We find that Yorkie (Yki), the Drosophila homolog of the Hippo pathway transducer, Yap, regulates the transcription of Myc, and that Myc functions as a critical cellular growth effector of the pathway. We demonstrate that in turn, Myc regulates the expression of Yki as a function of its own cellular level, such that high levels of Myc repress Yki expression through both transcriptional and post-transcriptional mechanisms. We propose that the co-dependent regulatory relationship functionally coordinates the cellular activities of Yki and Myc and provides a mechanism of growth control that regulates organ size and has broad implications for cancer.
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