Biochemical and mutagenic analysis of the melanoma tumor suppressor gene product/p16.

摘要: P16 was originally discovered by its ability to interact with CDK4 and specifically inhibit the catalytic activity of CDK4/D1 kinase. Increased attention has focused on p16 gene because location chromosome 9p21, a region involved in chromosomal rearrangements large number tumor types. The is also mutated cell lines primary cells. Furthermore, linkage analysis studies suggest that familial melanoma susceptibility. Due oncogenic potential mutations this suppressor, it important identify characterize those which alter activity. We have performed systematic associated mutants generated charge Ala mutagenesis. Using microtiter plate assays measure both p16-cdk4 binding cdk4/D1 kinase activity, we show here are defective, as some mutants. These results support idea mutation, via deregulation pathway, biological significance development melanoma. defined within molecule changes likely result defective protein.