Smurf1 restricts the antiviral function mediated by USP25 through promoting its ubiquitination and degradation

Journal Article · Sun Apr 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.03.015· OSTI ID:23137229

Qian, Guanghui; Hu, Xiaohan; Li, Gen; Ding, Yueyue ^[1]; Zhu, Liyan ^[2]; others, and

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1. Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, 215025 (China)
2. School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123 (China)

Highlights: • Smurf1 decreases USP25 protein turnover. • The E3 ligase enzymatic activity of Smurf1 is required for USP25 degradation. • Smurf1 promotes the K48-linkage polyubiquitination of USP25. • Smurf1 negatively regulated the antiviral function mediated by USP25. Protein ubiquitination and deubiquitination enzymes are widely involved in innate immune responses. The ubiquitin specific protease 25 (USP25), a deubiquitinating enzyme, has been demonstrated to play an important role in virus infection and immunity. However, how USP25 is degraded and regulated by E3 ubiquitin ligases remains poorly understood. Here, we identified Smad ubiquitin regulatory factor 1(Smurf1) as a first novel E3 ubiquitin ligase of USP25. Smurf1 overexpression decreases USP25 protein turnover, and the E3 ligase enzymatic activity of Smurf1 is required for USP25 degradation. Additionally, Smurf1-mediated degradation of USP25 is via promoting the K48-linkage polyubiquitination of USP25 in an ubiquitin proteasome dependent pathway. Importantly, USP25 overexpression restricts vesicular stomatitis virus (VSV) replication and the restriction of VSV replication by USP25 is enhanced in Smurf1 stable knock down cells. Therefore, our study firstly identified that Smurf1 negatively regulated the antiviral function mediated by USP25. Our findings revealed a previously unrecognized role of Smurf1 acting on USP25 and also their roles in the regulation of VSV replications.

• OSTI ID: 23137229
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 498; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
IMMUNITY
LIGASES
VIRUSES