The Steroid Hormone 20-Hydroxyecdysone Promotes the Cytoplasmic Localization of Yorkie to Suppress Cell Proliferation and Induce Apoptosis
The Steroid Hormone 20-Hydroxyecdysone Promotes the Cytoplasmic Localization of Yorkie to Suppress Cell Proliferation and Induce Apoptosis
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类固醇激素20-羟基蜕皮酮促进约克夏细胞质定位，抑制细胞增殖并诱导细胞凋亡
DOI：
10.1074/jbc.m116.719856
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发表时间：
2016-10-07
影响因子：
4.8
通讯作者：
Zhao, Xiao-Fan
中科院分区：
文献类型：
--
作者：
Wang, Di;Li, Xiang-Ru;Zhao, Xiao-Fan
转录共激活因子Yki（Yorkie）是Hippo通路的成员，根据其在细胞核或细胞质中的位置来调节细胞增殖或凋亡。然而，调节Yki亚细胞定位的上游因子尚不清楚。我们发现类固醇激素20 - 羟基蜕皮酮（20E）诱导Yki磷酸化，使其留在细胞质中，从而促进鳞翅目昆虫棉铃虫中肠的凋亡。Yki在多种组织中表达，在变态蜕皮早期在表皮和中肠中表达增加。Yki主要定位于取食幼虫中肠细胞的细胞核，但在变态蜕皮幼虫中肠细胞中主要定位于细胞质。在取食幼虫中敲低Yki促进幼虫 - 蛹的转变、中肠程序性细胞死亡，并抑制IAP1（凋亡抑制因子1）的表达。在表皮细胞系（HaEpi）中敲低Yki诱导Caspase3/7活性增加。在HaEpi细胞中过表达的Yki主要定位于细胞核并诱导细胞增殖。20E促进Yki的细胞质定位，降低IAP1的表达，导致凋亡。20E通过提高Yki磷酸化水平以及促进Yki与衔接蛋白14 - 3 - 3 - E之间的相互作用来促进Yki在细胞质中的滞留。这种对Yki的调节抑制细胞增殖并诱导细胞凋亡。
The transcriptional co-activator Yki (Yorkie), a member of the Hippo pathway, regulates cell proliferation or apoptosis, depending on its nuclear or cytoplasmic location. However, the upstream factors regulating the subcellular localization of Yki are unclear. We found that the steroid hormone 20-hydroxyecdysone (20E) induces phosphorylation of Yki, causing it to remain in the cytoplasm, where it promotes apoptosis in the midgut of the lepidopteran insect Helicoverpa armigera. Yki is expressed in various tissues, with an increase in the epidermis and midgut during early metamorphic molting. Yki is localized mainly in the nucleus of feeding larval midgut cells but is mainly localized in the cytoplasm of metamorphic molting larval midgut cells. The knockdown of Yki in the feeding larvae promotes larval-pupal transition, midgut programmed cell death, and repressed IAP1 (inhibitor of apoptosis 1) expression. Knockdown of Yki in the epidermal cell line (HaEpi) induced increased activation of Caspase3/7. Overexpressed Yki in HaEpi cells was mainly localized in the nucleus and induced cell proliferation. 20E promotes the cytoplasmic localization of Yki, reducing the expression of the IAP1, resulting in apoptosis. 20E promotes cytoplasmic retention of Yki by increasing Yki phosphorylation levels and promoting the interaction between Yki and the adaptor protein 14-3-3-E. This regulation of Yki suppresses cell proliferation and induces cell apoptosis.