Cdk4

GWB-BE2683

A synthetic peptide corresponding to residues on the N-terminus of human CDK4 was used as an immunogen.

WB: 1:500FC: 1:60IP: 1:30. Cyclin dependent kinases (CDK\' s) are kinases that interact with cyclins and regulate cell division. There is evidence that phosphorylation of the C-terminal region of Rb by Cdk4/6 initiates successive intramolecular interactions between the C-terminal region and the central pocket. The initial interaction displaces histone deacetylase from the pocket blocking active transcriptional repression by Rb. These intramolecular interactions provide a molecular basis for sequential phosphorylation of Rb by Cdk4/6 and Cdk2. Cdk4/6 is activated early in G1 blocking active repression by Rb (1). In primary epidermal cells it has been found that oncogenic Ras transiently decreases cyclin-dependent kinase (CDK) 4 expression in association with cell cycle arrest in G1 phase. CDK4 co-expression circumvents Ras growth suppression and induces invasive human neoplasia resembling squamous cell carcinoma. Tumorigenesis is dependent on CDK4 kinase function with cyclin D1 required but not sufficient for this process. These data identify a new role for oncogenic Ras in CDK4 regulation and highlight the functional importance of CDK4 suppression in preventing uncontrolled growth (2). 1. Harbour JW et al. Cell 98(6):859-69. 19992. Lazaroy M et al. Nat Med 8(10):1105-14 20023. Manufactured under U. S. Patents No. 5 675 063 and 7 429 487