Nucleolar Arf sequesters Mdm2 and activates p53

被引：757

作者：

Weber, JD

Taylor, LJ

Roussel, MF

Sherr, CJ

Bar-Sagi, D

机构：

[1] St Jude Childrens Res Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Memphis, TN 38105 USA

[3] SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

来源：

NATURE CELL BIOLOGY | 1999年 / 1卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/8991

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Ink4/Arf locus encodes two tumour-suppressor proteins, p16(ink4a) and p19(Arf), that govern the antiproliferative functions of the retinoblastoma and p53 proteins, respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts undergo replicative senescence. These topological interactions of Arf and Mdm2 point towards a new mechanism for p53 activation.

引用

页码：20 / 26

页数：7

共 39 条

[11] Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53 [J].