title: Identification of CDK4 as a target of c-MYC.
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.
authors.affiliation: Howard Hughes Medical Institute, The Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, 424 North Bond Street, Baltimore, MD 21231, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hermeking
authors.forename: C
authors.initials: C
authors.lastname: Rago
authors.forename: M
authors.initials: M
authors.lastname: Schuhmacher
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: J F
authors.initials: JF
authors.lastname: Barrett
authors.forename: A J
authors.initials: AJ
authors.lastname: Obaya
authors.forename: B C
authors.initials: BC
authors.lastname: O'Connell
authors.forename: M K
authors.initials: MK
authors.lastname: Mateyak
authors.forename: W
authors.initials: W
authors.lastname: Tam
authors.forename: F
authors.initials: F
authors.lastname: Kohlhuber
authors.forename: C V
authors.initials: CV
authors.lastname: Dang
authors.forename: J M
authors.initials: JM
authors.lastname: Sedivy
authors.forename: D
authors.initials: D
authors.lastname: Eick
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D018076:DNA, Complementary; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C495900:CDK4 protein, human; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases