Effects of P27/Bmdacapo, in the CIP/KIP family, on cell proliferation, growth and development in the silkworm (Bombyx mori)

Gene. 2019 Jun 5:700:31-37. doi: 10.1016/j.gene.2019.02.087. Epub 2019 Mar 19.

Abstract

We investigated changes in expression of the CIP/KIP family-related genes and the cycle-dependent factors Pcna, Cdk4 and Cdk2 during the growth and development of mice, Drosophila and silkworms. When the organism was in a period of rapid development, the related genes of the CIP/KIP family had low expression level and the cell cycle-dependent genes were highly expressed. In mammals, the CIP/KIP family includes three genes, p21, p27/Dacapo and p57. However, only one gene, P27/Dacapo, exists in the CIP/KIP family in silkworm and the orthologous gene in the silkworm is named Bmdacapo. Down-regulation of Bmdacapo in silkworm embryos caused overdevelopment of the embryos and indicated that Bmdacapo can inhibit silkworm growth and development. Up-regulation of Bmdacapo in silkworm cells inhibited cell proliferation, whereas down-regulation of Bmdacapo promoted cell proliferation. In order to explore the mechanism of Bmdacapo regulated silkworm development and cell proliferation, the effect of Bmdacapo on cell cycle changes was examined. The results demonstrate that Bmdacapo was able to induce G1/S phase arrest in the cell cycle. In silkworm cells, Bmdacapo inhibits the expression of Pcna, CDK4 and CDK2, which affects the cell cycle and ultimately inhibits cell proliferation. This regulatory mechanism is particularly different from mammals.

Keywords: CIP/KIP family; Cell cycle; Development; G1/S; P27/Dacapo; Silkworm.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bombyx / cytology
  • Bombyx / embryology*
  • Bombyx / metabolism
  • Cell Cycle
  • Cell Proliferation
  • Cells, Cultured
  • Cloning, Molecular
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Embryonic Development
  • Gene Expression Regulation, Developmental
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • dap protein, Drosophila
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4