泛素特异性蛋白酶USP28是MYC稳定性所必需的。

The ubiquitin-specific protease USP28 is required for MYC stability.

作者信息

Popov Nikita, Wanzel Michael, Madiredjo Mandy, Zhang Dong, Beijersbergen Roderick, Bernards Rene, Moll Roland, Elledge Stephen J, Eilers Martin

机构信息

Institute of Molecular Biology and Tumor Research, Emil-Mannkopff-Str.2, 35033 Marburg, Germany.

出版信息

Nat Cell Biol. 2007 Jul;9(7):765-74. doi: 10.1038/ncb1601. Epub 2007 Jun 10.

DOI:10.1038/ncb1601

PMID:17558397

Abstract

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 FBW7alpha, 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 FBW7gamma. High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation.

摘要

MYC原癌基因编码一种转录因子，该转录因子与许多人类肿瘤的发生有关。在此，我们使用条形码短发夹RNA（shRNA）筛选来鉴定MYC功能所需的多个基因。其中一个基因编码USP28，一种泛素特异性蛋白酶。USP28是人类肿瘤细胞中MYC稳定性所必需的。USP28通过与FBW7α相互作用与MYC结合，FBW7α是一种F-box蛋白，是SCF型泛素连接酶的一部分。因此，它在细胞核中稳定MYC，但在核仁中则不然，在核仁中MYC被FBW7γ降解。在结肠癌和乳腺癌中发现USP28的高表达水平，并且USP28对MYC的稳定作用对于肿瘤细胞增殖至关重要。