Cyclin-dependent kinase regulatory subunit 1 promotes cell proliferation by insulin regulation

Abstract

These authors contributed equally to this work.Keywords: body size, cell proliferation, CKS1, insulin, midgut Cyclin-dependent kinase regulatory subunit 1 (CKS1) helps regulate the cell cycle to increase cell number. However, the hormonal regulation on CKS1 expression is not well understood. We report that CKS1 is involved in the promotion of cell proliferation with insulin regulation in the lepidopteran insect Helicoverpa armigera. CKS1 is expressed in various tissues during the larval feeding stage. CKS1 knockdown results in larval death, body weight decrease, pupation time delay, and small-sized pupa formation. The underlying mechanism involves the blocking of cell proliferation and the repression of gene expression in the insulin pathway after CKS1 knockdown. CKS1 overexpression in the epidermal cell line results in cell proliferation. The N45 amino acid asparagine in the CKS domain is essential for the function of CKS in cell proliferation. CKS1 is upregulated by insulin via an insulin receptor, but is repressed by a high level of steroid hormone 20-hydroxyecdysone (20E). Results suggest that CKS1 promotes cell proliferation and body growth in coordination with the regulatory actions of insulin and steroid hormone 20E.

20-hydroxyecdysone activates Forkhead box O to promote proteolysis during Helicoverpa armigera molting

“…The lack of a juvenile hormoneproducing organ, the corpora allata, elevates FoxO activity and results in small pupae . Higher concentrations of 20E repress insulin-induced gene expression in H. armigera (Liu et al, 2015). In Drosophila, FoxO interacts with USP to mediate ecdysone biosynthesis .…”

Protein kinase C delta phosphorylates ecdysone receptor B1 to promote gene expression and apoptosis under 20-hydroxyecdysone regulation

“…In Drosophila melanogaster, 20E also stops stem cell proliferation (10). In Helicoverpa armigera, 20E causes a switch from autophagy to apoptosis (11), counteracts the action of insulin (12), promotes phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) expression (13), and promotes the Hippo pathway to induce apoptosis (14). Furthermore, 20E is used as a food additive to maintain the glucose-lipid balance in humans, without the side effects of mammalian hormones (15).…”

The Steroid Hormone 20-Hydroxyecdysone Promotes the Cytoplasmic Localization of Yorkie to Suppress Cell Proliferation and Induce Apoptosis

“…Our study also showed that nuclear-located Yki prevents apoptosis and upregulates IAP1 expression. A previous study indicated that the H. armigera larval midgut cells are proliferating at the sixth instar 48-h stage but undergo apoptosis at the sixth instar 96-h stage (18). Therefore, the knockdown of Yki in sixth instar 6-h larvae would block cell proliferation, accelerating the 20E-mediated midgut apoptosis and larval-pupal transition.…”