c-JUN prevents methylation of p16(INK4a) (and Cdk6): the villain turned bodyguard

Oncotarget. 2011 May;2(5):422-7. doi: 10.18632/oncotarget.279.


A novel way by which the AP-1 factor c-JUN interferes with tumorigenesis has recently been elucidated [1]. In a model of murine leukemia, c-JUN prevents the epigenetic silencing of the cell cycle kinase CDK6. In the absence of c-JUN, CDK6 is down-regulated and the 5’region of the gene is methylated. Down-regulation of CDK6 results in significantly delayed leukemia formation. Here we show that c-JUN is also involved in protecting the promoter region of the tumor suppressor p16(INK4a), which is consistently methylated over time in c-JUN deficient cells. In cells expressing c-JUN, p16(INK4a) promoter methylation is a less frequent event. Our study unravels a novel mechanism by which the AP-1 factor c-JUN acts as a “bodyguard”,and preventing methylation of a distinct set of genes after oncogenic transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Methylation*
  • Disease Models, Animal
  • Disease Progression
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Silencing
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Leukemia / genetics*
  • Leukemia / physiopathology
  • Mice
  • Mutant Proteins / genetics
  • Promoter Regions, Genetic / genetics


  • Cyclin-Dependent Kinase Inhibitor p16
  • Mutant Proteins
  • Cyclin-Dependent Kinase 6
  • JNK Mitogen-Activated Protein Kinases