c-JUN prevents methylation of p16INK4a (and Cdk6): the villain turned bodyguard
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1Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria
2Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer, Medical University of Vienna (MUV), Vienna, Austria
Keywords: AP-1, CDK6, p16, leukemia
Received: May 27, 2011; Accepted: May 28, 2011; Published: May 28, 2011;
Karoline Kollmann, e-mail:
A novel way by which the AP-1 factor c-JUN interferes with tumorigenesis has recently been elucidated . 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 p16INK4a, which is consistently methylated over time in c-JUN deficient cells. In cells expressing c-JUN, p16INK4a 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.
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