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.
Highlights
AP-1 (Activator Protein-1) transcription factors are basic leucine-zipper proteins [2,3,4,5]
Conclusion c-JUN is a common regulator of cell cycle components that has been described to have a direct role in regulating the transcription of p53 and CyclinD1
Based on our studies we postulate a novel mechanism for how c-JUN accelerates leukemogenesis and regulates genes required for cell cycle progression in tumor cells
Summary
AP-1 (Activator Protein-1) transcription factors are basic leucine-zipper (bZIP) proteins [2,3,4,5]. AP-1 is able to modulate opposing functions, such as promoting or suppressing tumor development. C) Immunoblot for c-JUN and p16INK4a of c-JunΔ/Δ and c-Junfl/fl cells after 12, 24, 36 and 48 hours of Aza-dC treatment. C-JUN negatively regulates the transcription of p53 in MEFs by direct binding to the promoter region of p53.
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