AKT-dependent phosphorylation of Niban regulates nucleophosmin- and MDM2-mediated p53 stability and cell apoptosis

被引:58
作者
Ji, Haitao [1 ,2 ]
Ding, Zhiyong [3 ]
Hawke, David [4 ]
Xing, Dongming [5 ]
Jiang, Bing-Hua [6 ]
Mills, Gordon B. [3 ]
Lu, Zhimin [1 ,2 ,7 ,8 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[5] Tsinghua Univ, Lab Pharmaceut Sci, Sch Life Sci, Beijing 100084, Peoples R China
[6] Nanjing Med Univ, Ctr Canc, Dept Pathol, Nanjing 210029, Jiangsu, Peoples R China
[7] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA
[8] Univ Texas Houston, Grad Sch Biomed Sci Houston, Houston, TX 77030 USA
关键词
Niban; AKT; nucleophosmin; p53; MDM2; apoptosis; TUMOR-SUPPRESSOR PROTEIN; PI3K/AKT PATHWAY; BETA-CATENIN; CANCER; ACTIVATION; GENE; DEGRADATION; MECHANISMS; EXPRESSION; INHIBITOR;
D O I
10.1038/embor.2012.53
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although Niban is highly expressed in human cancer cells, the cellular functions of Niban remain largely unknown. We demonstrate here that ultraviolet irradiation induces phosphorylation of Niban at S602 by AKT, which increases the association of Niban with nucleophosmin and disassociation of nucleophosmin from the MDM2 complex. This leads to the promotion of MDM2-p53 interaction and subsequent p53 degradation, thereby providing an antiapoptotic effect. Conversely, depletion of or deficiency in Niban expression promotes stabilization of p53 with increased cell apoptosis. Our findings illustrate a pivotal role for AKT-mediated phosphorylation of Niban in protecting cells from genotoxic stress-induced cell apoptosis.
引用
收藏
页码:554 / 560
页数:7
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