Identification of CDK4 as a target of c-MYC

The prototypic oncogene c-MYC encodes a transcription factor that can drive proliferation by promoting cell-cycle reentry. However, the mechanisms thr ough which c-MYC achieves these effects have been unclear. Using serial ana lysis 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 inc rease in CDK4 mRNA levels through four highly conserved c-MYC binding sites within the CDK4 promoter. Cell-cycle progression is delayed in c-MYC-defic ient RAT1 cells, and this delay was associated with a defect in CDK4 induct ion. Ectopic expression of CDK4 in these cells partially alleviated the gro wth defect. Thus, CDK4 provides a direct link between the oncogenic effects of c-MYC and cell-cycle regulation.