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

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

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at https://doi.org/10.1128/MCB.00320-17.

ACKNOWLEDGMENTS

This study was supported by grants from the National Natural Science Foundation of China (grants no. 31501120, 81602738, and 81602498); Joint Funds for the Innovation of Science and Technology, Fujian Province (grant no. 2016Y9040); the Natural Science Foundation of Fujian Province (grants no. 2015J05065 and 2015J05157); the Health and Family Planning Commission of Fujian Province (grants no. 2016-ZQN-65, 2014-1-38, and 2016-1-40); the Educational Scientific Research Project of Young Teachers of Fujian Province (grants no. JA14131, JA14140, and JAT160216); the Outstanding Youth Scientific Research Personnel Training Program at Fujian Province University (grant no. 2016B023); the Scientific Research Project of Young Teachers of Fujian Medical University (grants no. 2014MP002 and 2014MP001); and the Setting Sail Foundation of Fujian Medical University (grant no. 2016QH006).

We declare that we have no conflicts of interest with the contents of this article.