Larsen C J
IBMIG, Poitiers.
Bull Cancer. 1998 Jun;85(6):523-6.
In man, the MTS1 (multiple tumor suppressor 1) locus has been located on chromosome band 9p21 and encodes two unrelated genes, p16INK4a and p19ARF that both act, through different mechanisms, as cell proliferation inhibitors. The inhibitory mechanism of p19ARF has begun to be elucidated by the finding that the protein has the ability to bind the mdm2 oncoprotein. mdm2 is implicated in the degradation of p53 and its functional inactivation. While this result provides an opportunity for understanding the tumor suppression role of p19ARF, it allows to define a new cell cycle regulatory pathway, the p19ARF-p53 pathway. In this respect, MTS1 is unique in its ability to control two crucial pathways that regulate the cell cycle. For this reason, it will be crucial to investigate the status of p19ARF in a variety human tumors.
在人类中,MTS1(多重肿瘤抑制因子1)基因座位于9号染色体的9p21带,编码两个不相关的基因,即p16INK4a和p19ARF,它们均通过不同机制作为细胞增殖抑制剂发挥作用。通过发现p19ARF蛋白具有结合mdm2癌蛋白的能力,其抑制机制已开始得到阐明。mdm2与p53的降解及其功能失活有关。虽然这一结果为理解p19ARF的肿瘤抑制作用提供了契机,但它也有助于定义一条新的细胞周期调控途径,即p19ARF-p53途径。在这方面,MTS1在控制两条调节细胞周期的关键途径的能力方面是独一无二的。因此,研究p19ARF在多种人类肿瘤中的状态至关重要。