The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis
The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis
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DOI：
10.1016/s0092-8674(03)00557-9
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发表时间：
2003-08-22
期刊：
影响因子：
64.5
通讯作者：
Hariharan, IK
中科院分区：
文献类型：
--
作者：
Harvey, KF;Pfleger, CM;Hariharan, IK
建立和维持体内平衡对生物体的健康至关重要，它是由细胞增殖和死亡的平衡决定的。两个共同调节果蝇生长、增殖和凋亡的基因是编码丝氨酸/苏氨酸激酶的疣（wts）和编码含有wts相互作用蛋白的WW结构域的萨尔瓦多（sav）。然而，sav和wts调控细胞生长和凋亡的机制尚不清楚。在这里，我们描述了河马（hpo）的突变，它编码一种与哺乳动物Mst1和Mst2最相关的蛋白激酶。与wts和sav一样，hpo突变导致组织生长增加和细胞凋亡受损，其特征是细胞周期调节因子cyclin E和细胞凋亡抑制剂DIAP1水平升高。Hpo， Sav和Wts在物理和功能上相互作用，并调节DIAP1水平，可能通过Hpo介导的磷酸化和随后的降解。因此，Hpo将Sav和Wts与细胞凋亡的关键调节因子联系起来。
Establishing and maintaining homeostasis is critical to the well-being of an organism and is determined by the balance of cell proliferation and death. Two genes that function together to regulate growth, proliferation, and apoptosis in Drosophila are warts (wts), encoding a serine/threonine kinase, and salvador (sav), encoding a WW domain containing Wts-interacting protein. However, the mechanisms by which sav and wts regulate growth and apoptosis are not well understood. Here, we describe mutations in hippo (hpo), which encodes a protein kinase most related to mammalian Mst1 and Mst2. Like wts and sav, hpo mutations result in increased tissue growth and impaired apoptosis characterized by elevated levels of the cell cycle regulator cyclin E and apoptosis inhibitor DIAP1. Hpo, Sav, and Wts interact physically and functionally, and regulate DIAP1 levels, likely by Hpo-mediated phosphorylation and subsequent degradation. Thus, Hpo links Sav and Wts to a key regulator of apoptosis.