Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein
Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein
复制标题
泛素特异性蛋白酶 USP6 调节 c-Jun 蛋白的稳定性
DOI：
10.1128/mcb.00320-17
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发表时间：
2018-01-01
影响因子：
5.3
通讯作者：
Lin, Dexin
中科院分区：
文献类型：
--
作者：
Li, Lisheng;Yang, Hong;Lin, Dexin
摘要c-Jun基因编码的转录因子参与了许多生理和病理过程。c-Jun是一种高度不稳定的蛋白质，通过泛素化/蛋白酶体依赖性机制降解。然而，调节c-Jun蛋白稳定性的去泛素化酶（DUB）需要进一步研究。在这里，通过筛选DUB表达文库，我们鉴定了泛素特异性蛋白酶6（USP 6），并表明它以取决于其酶活性的方式调节c-Jun蛋白的稳定性。USP 6与c-Jun相互作用并拮抗其泛素化。USP 6过表达上调c-Jun/AP-1介导的下游信号通路的活性并促进细胞侵袭。此外，在USP 6易位结节性筋膜炎中上调的许多异常基因是c-Jun调节的重要潜在靶点。根据我们的数据，USP 6是一种去泛素化c-Jun并调节其下游细胞功能的酶。
ABSTRACT The c-Jun gene encodes a transcription factor that has been implicated in many physiological and pathological processes. c-Jun is a highly unstable protein that is degraded through a ubiquitination/proteasome-dependent mechanism. However, the deubiquitinating enzyme (DUB) that regulates the stability of the c-Jun protein requires further investigation. Here, by screening a DUB expression library, we identified ubiquitin-specific protease 6 (USP6) and showed that it regulates the stability of the c-Jun protein in a manner depending on its enzyme activity. USP6 interacts with c-Jun and antagonizes its ubiquitination. USP6 overexpression upregulates the activity of the downstream signaling pathway mediated by c-Jun/AP-1 and promotes cell invasion. Moreover, many aberrant genes that are upregulated in USP6 translocated nodular fasciitis are great potential targets regulated by c-Jun. Based on our data, USP6 is an enzyme that deubiquitinates c-Jun and regulates its downstream cellular functions.