Tumor suppression by Ink4a-Arf: progress and puzzles

Curr Opin Genet Dev. 2003 Feb;13(1):77-83. doi: 10.1016/s0959-437x(02)00013-8.


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.

Publication types

  • Review

MeSH terms

  • ADP-Ribosylation Factors / physiology
  • Animals
  • Cyclin-Dependent Kinase Inhibitor p16 / physiology*
  • Feedback, Physiological / physiology
  • Humans
  • Lymphoma / metabolism
  • Mice
  • Neoplasms / prevention & control*
  • Rats
  • Retinoblastoma Protein / physiology
  • Tumor Suppressor Protein p53 / physiology


  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • ADP-Ribosylation Factors