Identification of CDK4 as a target of c-MYC

H Hermeking, C Rago… - Proceedings of the …, 2000 - National Acad Sciences
H Hermeking, C Rago, M Schuhmacher, Q Li, JF Barrett, AJ Obaya, BC O'Connell…
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
The prototypic oncogene c-MYC encodes a transcription factor that can drive proliferation by
promoting cell-cycle reentry. However, the mechanisms through which c-MYC achieves
these effects have been unclear. Using serial analysis of gene expression, we have
identified the cyclin-dependent kinase 4 (CDK4) gene as a transcriptional target of c-MYC. c-
MYC induced a rapid increase in CDK4 mRNA levels through four highly conserved c-MYC
binding sites within the CDK4 promoter. Cell-cycle progression is delayed in c-MYC …
The prototypic oncogene c-MYC encodes a transcription factor that can drive proliferation by promoting cell-cycle reentry. However, the mechanisms through which c-MYC achieves these effects have been unclear. Using serial analysis of gene expression, we have identified the cyclin-dependent kinase 4 (CDK4) gene as a transcriptional target of c-MYC. c-MYC induced a rapid increase in CDK4 mRNA levels through four highly conserved c-MYC binding sites within the CDK4 promoter. Cell-cycle progression is delayed in c-MYC-deficient RAT1 cells, and this delay was associated with a defect in CDK4 induction. Ectopic expression of CDK4 in these cells partially alleviated the growth defect. Thus, CDK4 provides a direct link between the oncogenic effects of c-MYC and cell-cycle regulation.
National Acad Sciences