Oncotarget

Research Perspectives:

c-JUN prevents methylation of p16INK4a (and Cdk6): the villain turned bodyguard

Karoline Kollmann _, Gerwin Heller, Veronika Sexl

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Oncotarget. 2011; 2:422-427. https://doi.org/10.18632/oncotarget.279

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Abstract

Karoline Kollmann1, Gerwin Heller2, Veronika Sexl1

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;

Correspondence:

Karoline Kollmann, e-mail:

Abstract

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 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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