Over-expression of cyclin D1 regulates Cdk4 protein synthesis.

Academic Article

Abstract

  • Increased Cdk4 expression occurs coincident with over-expression of cyclin D1 in many human tumours and tumourigenic mouse models. Here, we investigate both in vivo and in vitro the mechanism by which Cdk4 expression is regulated in the context of cyclin D1 over-expression. Cdk4 mRNA levels in cyclin D1-over-expressing tissue and cultured cells were unchanged compared with controls. In contrast, Cdk4 protein levels were increased in cyclin D1-over-expressing tissue and cells versus their respective controls. This increase was not due to altered protein stability, but appeared to be due to an increase in Cdk4 protein synthesis. We also performed immunoprecipitation and in vitro kinase assays to demonstrate an increase in cyclin D1-Cdk4 complex formation and associated kinase activity. Blocking cyclin D1 expression resulted in diminished Cdk4 protein but not mRNA levels. These findings suggest a mechanism by which Cdk4 expression is increased in the context of cyclin D1 over-expression during tumourigenesis.
  • Published In

  • Cell Proliferation  Journal
  • Keywords

  • Animals, Cell Line, Transformed, Cyclin D1, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinases, Gene Expression Regulation, Enzymologic, Hepatocytes, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Proto-Oncogene Proteins, RNA, Messenger, Transduction, Genetic
  • Author List

  • Parker MA; Deane NG; Thompson EA; Whitehead RH; Mithani SK; Washington MK; Datta PK; Dixon DA; Beauchamp RD
  • Start Page

  • 347
  • End Page

  • 360
  • Volume

  • 36
  • Issue

  • 6