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Mol Cell Biol. 2017 Dec 29;38(2). pii: e00320-17. doi: 10.1128/MCB.00320-17. Print 2018 Jan 15.

Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein.

Li L#1,2, Yang H#3, He Y#3, Li T3, Feng J3, Chen W4, Ao L5,2, Shi X3, Lin Y6,2, Liu H3, Zheng E3, Lin Q3, Bu J3, Zeng Y3, Zheng M3,2, Xu Y3, Liao Z3, Lin J7,2, Lin D1.

Author information

1
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China lilisheng218@fjmu.edu.cn dexin100@mail.fjmu.edu.cn.
2
Strait Collaborative Innovation Center of Biomedicine and Pharmaceutics (SCIBP), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
3
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
4
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
5
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
6
Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
7
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
#
Contributed equally

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.

KEYWORDS:

USP6; c-Jun; deubiquitinating enzyme; deubiquitination; nodular fasciitis

PMID:
29061731
PMCID:
PMC5748463
DOI:
10.1128/MCB.00320-17
[Indexed for MEDLINE]
Free PMC Article

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