Cul4A physically associates with MDM2 and participates in the proteolysis of p53

被引：89
作者：
Nag, A
Bagchi, S
Raychaudhuri, P
机构：
[1] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA
[2] Univ Illinois, Coll Dent, Ctr Mol Biol Oral Dis, Chicago, IL 60607 USA
来源：
CANCER RESEARCH | 2004年 / 64卷 / 22期
关键词：
D O I：
10.1158/0008-5472.CAN-04-2598
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The cullin 4A (Cul4A) gene is amplified and overexpressed in breast and hepatocellular carcinomas. Cul4A functions as an E3 ligase and participates in the proteolysis of several regulatory proteins through the ubiquitin-proteasome pathway. Here, we show that Cul4A associates with MDM2 and p53. Depletion of Cul4A leads to an accumulation of p53. Moreover, expression of Cul4A increases the decay-rate of p53 and delays the accumulation of p53 in response to DNA damage. Cul4A fails to increase the decay of p53 in mouse embryonic fibroblasts lacking MDM2. In addition, the Cul4A-mediated rapid decay of p53 is blocked by p19ARF. The results provide evidence for a role of Cul4A in the MDM2-mediated proteolysis of p53.
引用
收藏
页码：8152 / 8155
页数：4
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