Regulation of INK4a/ARF gene locus and its role in cellular senescence

我们开发了一种生物发光成像系统，用于非侵入性和实时分析p16^&lt；ink4a&gt；在活体小鼠中的表达。利用这个系统，我们证明了在体内，各种致癌的侮辱通过降低DNMT1水平而引起p16^&lt；ink4a和gt；表达的表观遗传下调。这一途径在没有P53的情况下被加速，这表明P53通常控制着p16；Ink4a；反应。这些结果揭示了在p53失活的情况下，p16^&lt；Ink4a&gt；的备用肿瘤抑制作用，扩大了我们对肿瘤抑制机制是如何调控的理解。

We developed a bioluminescence imaging system for non-invasive and real-time analysis of p16^<Ink4a> expression in living mice. Using this system, we show that various oncogenic insults provoke epigenetic de-repression of p16^<Ink4a> expression through reduction of DNMT1 levels in vivo. This pathway is accelerated in the absence of p53, indicating that p53 normally holds the p16^<Ink4a> response in check. These results unveil a backup tumor suppressor role for p16^<Ink4a>in the event of p53 inactivation, expanding our understanding of how tumor suppression mechanism is regulated.