Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all

Nat Rev Mol Cell Biol. 2006 Sep;7(9):667-77. doi: 10.1038/nrm1987.


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, known as ARF. All three products participate in major tumour suppressor networks that are disabled in human cancer and influence key physiological processes such as replicative senescence, apoptosis and stem-cell self-renewal. Transcription from the locus is therefore kept under strict control. Mounting evidence suggests that although the individual genes can respond independently to positive and negative signals in different contexts, the entire locus might be coordinately suppressed by a cis-acting regulatory domain or by the action of Polycomb group repressor complexes.

Publication types

  • Review

MeSH terms

  • ADP-Ribosylation Factors / genetics*
  • Animals
  • Apoptosis / genetics
  • Cellular Senescence / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Gene Expression Regulation / genetics*
  • Humans
  • Polycomb-Group Proteins
  • Quantitative Trait Loci / genetics*
  • Repressor Proteins / genetics
  • Signal Transduction / genetics
  • Stem Cells / physiology*


  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Polycomb-Group Proteins
  • Repressor Proteins
  • ADP-Ribosylation Factors