Tumor suppression by Ink4a–Arf: progress and puzzles

Abstract

The two products of the Ink4a–Arf locus, p16 Ink4a and p19 Arf (p14 ARF in humans), are potent tumor suppressors that regulate the activities of the retinoblastoma protein and the p53 transcription factor. These proteins form part of a signaling network that is disrupted in most, if not all, cancer cells. The Ink4a-Arf locus responds to stress signals, limiting cell proliferation and modulating oncogene-induced apoptosis. Recent evidence emerging from mouse tumor models distinguishes the activities of p16 Ink4a and p19 Arf in regulating tumor onset and identifies differences in their responsiveness to drugs.