p16 Tumor Suppressor

p16, a protein named for its migration rate on denaturing gels, is a member of a class of functionally similar proteins called cyclin-dependent kinase inhibitors (CDKI). p16 and its relatives bind to CDKs and inhibit their kinase activity. Because cyclins and CDKs form the core of the cell cycle apparatus, p16 is positioned to directly regulate some of the most basic cell cycle decisions. In eukaryotic cells, the cell cycle is typically described in terms of four component phases: G1, S, G2, and M. Most regulation occurs at the G1—S and G2—M transitions. In higher eukaryotes, the G1 checkpoint is especially important. This is precisely where p16 acts, and its activity is biochemically and functionally linked to other regulators of the G1—S transition, including the wellknown cell cycle regulator (and tumor suppressor protein), Rb.