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

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.