| The INK4 family of cyclin dependent kinase inhibitors is one of the groups of proteins responsible for pRb-dependent arrest of the cell cycle at the G1/S boundary. The four members, p15 (INK4b), p16 (INK4a), p18 (INK4c), and p19 (INK4d) are almost biochemically indistinguishable in their ability to bind cyclin dependent kinases CDK4 and CDK6, which is mediated through binding to the INK4 ankyrin domain area. p16 and p15 have been shown to function as tumor suppressors and are often dysregulated in cancer through promoter methylation, point mutation or deletion. p18 and p19, conversely, are infrequently altered in cancer, are often expressed in cancer cells where p16 and p15 have been dysregulated and do not appear to function as tumor suppressors. Specific aims. (1) Identify unique binding partners to p18, p19 and p16; (2) determine if the C-terminal mediates these protein-protein interactions. (Abstract shortened by UMI.)... |
