The ARF tumor suppressor: structure, functions and status in cancer.

The INK4b-ARF-INK4a locus encodes two members of the INK4 family of cyclin-dependent kinase inhibitors, p15(INK4b) and p16(INK4a), and a completely unrelated protein called ARF. ARF is a nucleolar protein with unusual structure that exhibits tumor suppressive functions. There is growing evidence that ARF signaling is complex, and involves p53-dependent or -independent pathways aiming mainly at restraining abnormal cell growth and at maintaining genomic stability. As such, ARF is a critical component of tumor surveillance, and its expression is decreased in human tumors. In this review, we present the current knowledge on ARF regulation and major functions. The ARF status in human tumors is also briefly summarized.