ARF——一种新的抑癌因子的研究进展

Progress in The Tumor Suppressor, ARF

INK4a/ARF基因位于人染色体 9p2 1,是人类肿瘤中最常见的基因失活位点之一 .INK4a/ARF基因有两套各自独立的启动子 ,通过可变阅读框 ,能够编码两种蛋白质 :p16 INK4a和p14 ARF (ARF在鼠细胞中为p19ARF) .p16作为CDK4 /6的抑制因子 ,能够阻断pRb磷酸化 ,将细胞周期阻断在G1期 ;而ARF可结合原癌蛋白MDM2 ,稳定 p5 3,将细胞周期阻断在G1期和G2 /M转换期 ,或诱导细胞凋亡 .因此ARF蛋白和

The INK4a/ARF gene locus on human chromosome 9p21, is one of the most frequent targets of inactivating mutations in the human tumors. Containing two different promoters, INK4a/ARF can encode two distinct proteins in alternative reading frames, p16 INK4a and p14 ARF (the mouse homologues is called p19 ARF ). p16 is a recognized tumor suppressor that induces a G1 cell cycle arrest by inhibiting the phosphorylation of pRb by CDK4/6. While ARF inhibits oncoprotein MDM2, resulting in the stabilization of p53. These activities of ARF promote p53 mediated G1 and G2/M cell cycle arrests or apoptosis. So just like p16, the ARF protein also acts as a tumor suppressor.