p19^(ARF):INK4α编码的另一种细胞周期抑制蛋白

p19^(ARF): an alternative cellcycle repressor protein encoded by INK4α

INK4α的重叠编码框架编码产生出两个不同的蛋白p16INK4α和p19ARF。p19ARF在最近的研究中表明有细胞周期阻滞作用，它发挥作用时依赖于P53。其机制是通过与MDMZ结合并加速其降解，减少了后者对p53的下调，从而引起p53的积聚。p19ARF－MDM2－p53通路的发现对INK4α基因座的功能是个很好的补充。同时也提示INK4α基因突变或缺失可能同时损害p16INK4α－CDK4N6－RB和p19ARF－MDM2－p53这两条通路。一些肿瘤细胞中也发现确实存在p19ARF基因的失活。

The most frequently inactive tumor suppressor genes in human are p53 and INK4α.INK4α gene (also named MTS1, CDKN2) encode two unrelated proteins, designated as p16,INK4αand p19ARF respectively. Some recent researches show that P19ARF, like p16INK4α, is a potentcell-cycle suppressor and its function heavily relies on p53, the cellular gatelteeper for growth anddivision. The mechanism is that P19ARF can accelerate the decomposition of MDM2 by bindingwith it: leading to an accumulation of p53 protein, because MDM2 is a negative regulator ofp53. So, the revealing of p19ARF,-MDM2-p53 pathway is a good complement to the functionof INK4α gene, whose alteration may simultaneously impair both P16INK4α-CDK4, 6-RB andp19ARF,-MDM2-p53 pathway. Indeed, a variety of human tumors display the inactivity of P19ARFgene. This review mainly introduces the p19ARF gene's configuration, protein product and itsfunction.