title: c-JUN prevents methylation of p16(INK4a) (and Cdk6): the villain turned bodyguard.
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 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.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria. Karoline. Kollmann@vetmeduni.ac.at
authors.forename: Karoline
authors.initials: K
authors.lastname: Kollmann
authors.forename: Gerwin
authors.initials: G
authors.lastname: Heller
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004195:Disease Models, Animal; D018450:Disease Progression; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050505:Mutant Proteins; D051361:Cyclin-Dependent Kinase 6; D048031:JNK Mitogen-Activated Protein Kinases