The ubiquitin-specific protease USP28 is required for MYC stability

被引：376

作者：

Popov, Nikita

Wanzel, Michael

Madiredjo, Mandy

Zhang, Dong

Beijersbergen, Roderick

Bernards, Rene

Moll, Roland

Elledge, Stephen J.

Eilers, Martin

机构：

[1] Inst Mol Biol & Tumor Res, D-35033 Marburg, Germany

[2] Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

[3] Harvard Univ, Sch Med, Ctr Genet & Genom, Dept Genet, Boston, MA 02115 USA

[4] Univ Marburg, Dept Pathol, D-35033 Marburg, Germany

来源：

NATURE CELL BIOLOGY | 2007年 / 9卷 / 07期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ncb1601

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The MYC proto-oncogene encodes a transcription factor that has been implicated in the genesis of many human tumours. Here, we used a bar-code short hairpin RNA (shRNA) screen to identify multiple genes that are required for MYC function. One of these genes encodes USP28, an ubiquitin-specific protease. USP28 is required for MYC stability in human tumour cells. USP28 binds to MYC through an interaction with FBW7 alpha, an F-box protein that is part of an SCF-type ubiquitin ligase. Therefore, it stabilizes MYC in the nucleus, but not in the nucleolus, where MYC is degraded by FBW gamma.. High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation.

引用

收藏

页码：765 / U71

页数：28

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