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 genomicpathway by forming a transcription complex that binds to DNA with the help of the chaperoneproteins, heat shock proteins (Hsps) Hsc70 and Hsp90. However, the nongenomic mechanisms bywhich 20E regulates gene expression remain unclear. In this study,wefound that 20E regulated thephosphorylation of serine/threonine protein kinase cyclin-dependent kinase 10 (CDK10) througha 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 delayeddevelopment and suppressed 20E-induced gene transcription. CDK10 was localized to the nucleusvia its KKRR motif, and this nuclear localization and the ATPase motif were necessary for theefficient expression of the 20E-inducible gene. The rapid phosphorylation of CDK10 was inducedby 20E, whereas it was repressed by the inhibitors of G-protein-coupled receptors, phospholipaseC, and Ca2 +channels. Phosphorylated CDK10 exhibited increased interactions with Hsps Hsc70 andHsp90 and then promoted the interactions between Hsps and ecdysone receptor EcRB1 and thebinding 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 hormonereceptor 3 promoter. These results suggest that 20E induces CDK10 phosphorylation via a nongenomicpathway to regulate gene transcription in the nucleus. © 2014 by the Endocrine Society.