title: In a nongenomic action, steroid hormone 20-hydroxyecdysone induces phosphorylation of cyclin-dependent kinase 10 to promote gene transcription.
abstract: The insect steroid hormone 20-hydroxyecdysone (20E) regulates gene transcription via a genomic pathway by forming a transcription complex that binds to DNA with the help of the chaperone proteins, heat shock proteins (Hsps) Hsc70 and Hsp90. However, the nongenomic mechanisms by which 20E regulates gene expression remain unclear. In this study, we found that 20E regulated the phosphorylation of serine/threonine protein kinase cyclin-dependent kinase 10 (CDK10) through a nongenomic pathway to mediate gene transcription in the lepidopteran Helicoverpa armigera. The down-regulation of CDK10 by RNA interference in larvae and the epidermal cell line delayed development and suppressed 20E-induced gene transcription. CDK10 was localized to the nucleus via its KKRR motif, and this nuclear localization and the ATPase motif were necessary for the efficient expression of the 20E-inducible gene. The rapid phosphorylation of CDK10 was induced by 20E, whereas it was repressed by the inhibitors of G-protein-coupled receptors, phospholipase C, and Ca²⁺ channels. Phosphorylated CDK10 exhibited increased interactions with Hsps Hsc70 and Hsp90 and then promoted the interactions between Hsps and ecdysone receptor EcRB1 and the binding of the Hsps-EcRB1 complex to the 20E response element for the regulation of gene transcription. CDK10 depletion suppressed the formation of the Hsps-EcRB1 complex at the hormone receptor 3 promoter. These results suggest that 20E induces CDK10 phosphorylation via a nongenomic pathway to regulate gene transcription in the nucleus.
authors: The Key Laboratory of Plant Cell Engineering and Germplasm Innovation, Ministry of Education, Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors: Wen
authors: W
authors: Liu
authors: Mei-Juan
authors: MJ
authors: Cai
authors: Jin-Xing
authors: JX
authors: Wang
authors: Xiao-Fan
authors: XF
authors: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004441:Ecdysterone / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D007915:Lepidoptera / Q000187:drug effects* / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008675:Metamorphosis, Biological / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D011987:Receptors, Steroid / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D019476:Insect Proteins; D049990:Membrane Transport Modulators; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004441:Ecdysterone; D018844:Cyclin-Dependent Kinases