The regulation of INK4/ARF in cancer and aging

Loss of the INK4a/ARF/INK4b locus on chromosome 9p21 is among the most frequent cytogenetic events in human cancer. The products of the locus-p15(INK4b), p(16INK4a), and ARF-play widespread and independent roles in tumor suppression. Recent data also suggest that expression of p(16INK4a) induces an age-dependent decrease in the proliferative capacity of certain tissue-specific stem cells and unipotent progenitors. Here, we discuss the regulation and role of p(16INK4a), ARF, and p(15INK4b) in cancer and aging.