title: The Steroid Hormone 20-Hydroxyecdysone Promotes the Cytoplasmic Localization of Yorkie to Suppress Cell Proliferation and Induce Apoptosis.
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.
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Xiang-Ru
authors.initials: XR
authors.lastname: Li
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Du-Juan
authors.initials: DJ
authors.lastname: Dong
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Wang
authors.affiliation: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan 250100, China xfzhao@sdu.edu.cn.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D004441:Ecdysterone / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D007814:Larva / Q000235:genetics / Q000378:metabolism; D018978:Molting / Q000187:drug effects; D009036:Moths / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D015534:Trans-Activators; D004441:Ecdysterone
keywords: 20-hydroxyecdysone; Hippo pathway; Yorkie; apoptosis; cell proliferation; cytoplasmic localization; insect; steroid hormone