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The Steroid Hormone 20-Hydroxyecdysone Promotes the Cytoplasmic Localization of Yorkie to Suppress Cell Proliferation
Di Wang1, Xiang-Ru Li1, Du-Juan Dong1
1From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
Abstract:
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-ϵ. This regulation of Yki suppresses cell proliferation and induces cell apoptosis.
Insights
The steroid hormone 20-hydroxyecdysone (20E) controls Yorkie (Yki) localization in Helicoverpa armigera. This regulation by 20E promotes apoptosis by retaining Yki in the cytoplasm, impacting insect development.
Area of Science:
- Cell Biology
- Developmental Biology
- Insect Physiology
Background:
- The Hippo pathway's transcriptional co-activator Yorkie (Yki) controls cell proliferation and apoptosis.
- Upstream regulators of Yki's subcellular localization, crucial for its function, remain largely unknown.
- Yki plays a role in insect metamorphosis and tissue development.
Purpose of the Study:
- To investigate the upstream factors regulating the subcellular localization of Yki.
- To elucidate the role of the steroid hormone 20-hydroxyecdysone (20E) in Yki regulation.
- To understand how Yki localization impacts apoptosis and cell proliferation during insect development.
Main Methods:
- Investigated Yki expression and localization in Helicoverpa armigera midgut and epidermal cells during different developmental stages.
- Utilized knockdown and overexpression techniques for Yki in larval midgut and epidermal cell lines.
- Analyzed the effect of 20-hydroxyecdysone (20E) on Yki phosphorylation, localization, and interaction with 14-3-3-ϵ.
Main Results:
- 20-hydroxyecdysone (20E) induces Yki phosphorylation, leading to its cytoplasmic retention and promoting apoptosis in the midgut.
- Yki knockdown in feeding larvae accelerated metamorphosis, induced midgut apoptosis, and reduced inhibitor of apoptosis 1 (IAP1) expression.
- Yki knockdown in epidermal cells increased Caspase3/7 activation, while Yki overexpression induced cell proliferation.
- 20E enhances Yki phosphorylation and its interaction with 14-3-3-ϵ, suppressing proliferation and inducing apoptosis.
Conclusions:
- The steroid hormone 20E is a key upstream regulator of Yki localization and function in Helicoverpa armigera.
- 20E-mediated cytoplasmic retention of Yki is essential for inducing apoptosis and regulating metamorphosis.
- Yki's dynamic subcellular localization, controlled by hormonal cues, is critical for balancing cell proliferation and apoptosis during insect development.
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