Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. Two major classes of CDK inhibitors have been identified. The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. CDKIs are capable of suppressing growth, and several lines of evidence strongly suggest that at least some CDKIs may be tumor suppressor proteins.
p16-INK4A is the member of p16 family and is encoded by CDKN2A gene in humans. It has three isoforms, which are wildly expressed but not detected in brain or skeletal muscle, except that isoform 3 is pancreas-specific. Defects in p16INK4A are a cause of Li-Fraumeni syndrome (LFS) and melanoma-astrocytoma syndrome (MASTS).