Identification of CDK4 as a target of c-MYC

Heiko Hermeking, Carlo Rago, Marino Schuhmacher, Qing Li, John F. Barrett, Alvaro J. Obaya, Brenda C. O'Connell, Maria K. Mateyak, Wanny Tam, Franz Kohlhuber, Chi V. Dang, John M. Sedivy, Dirk Eick, Bert Vogelstein, Kenneth W. Kinzler

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2229-2234
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number5
DOIs
StatePublished - Feb 29 2000

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Cite this

Hermeking, H., Rago, C., Schuhmacher, M., Li, Q., Barrett, J. F., Obaya, A. J., O'Connell, B. C., Mateyak, M. K., Tam, W., Kohlhuber, F., Dang, C. V., Sedivy, J. M., Eick, D., Vogelstein, B., & Kinzler, K. W. (2000). Identification of CDK4 as a target of c-MYC. Proceedings of the National Academy of Sciences of the United States of America, 97(5), 2229-2234. https://doi.org/10.1073/pnas.050586197