Authors: Naoki Mori Rong Yang Norihiko Kawamata Carl W Miller Hideaki Mizoguchi H Phillip Koeffler
Publish Date: 2003/04/01
Volume: 77, Issue: 3, Pages: 259-262
Abstract
A mutation of the p16INK4abinding domain of the cyclin dependent kinase 4 CDK4 gene R24C has been reported in some cases of melanoma This mutation prevented binding of the CDK4 inhibitor p16INK4a to CDK4 To determine the relevance of the mutation we performed polymerase chain reactionsinglestrand conformation polymorphism PCRSSCP analysis in diverse types of human leukemias and solid tumors No mobility shifts indicating sequence alterations were observed in 273 tumors and 49 cell lines from diverse kinds of tumors These results suggest that in contrast to melanoma in many other types of human neoplasms the mutation of the CDK4 gene is very rare To better understand these findings we randomly mutagenized the CDK4 gene and used the yeast twohybrid method to screen for CDK4 mutants that had lost the ability to bind to p16INK4a Sequence analysis and in vitro kinase assays showed that most of the mutations that disrupted interactions with p16INK4a also knocked out the activity of CDK4This result may explain the rareness of CDK4 mutations in human tumors
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