p16INK4a is a member of the CDKN2 cyclin-dependent kinase inhibitor family of molecules. It is widely expressed (although not in skeletal muscle) and serves as a negative regulator of cell proliferation. The protein p16INK4A, identified as a negative regulator of the cell cycle, has been shown to bind to and inhibit the activity of the Cdk4/cyclin D complex. p19 ARF, which is unrelated to p16, arises from transcription of an alternative reading frame of the p16 gene. Like p16, p19 ARF has been shown to induce cell cycle arrest. Mice lacking p19 ARF but expressing functional p16 have been shown to develop tumors early in life.
