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Viruses. 2019 Jan 24;11(2). pii: E99. doi: 10.3390/v11020099.

PSMB1 Negatively Regulates the Innate Antiviral Immunity by Facilitating Degradation of IKK-ε.

Author information

1
Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, China. wufangyi_fd@163.com.
2
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai Academy of Science and Technology, Shanghai 201203, China. niuzhm@chgc.sh.cn.
3
Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, China. zhoubin1999fd@163.com.
4
Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, China. lipengcheng_fdu@163.com.
5
Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, China. fengqian@fudan.edu.cn.

Abstract

Proteasome is a large protein complex, which degrades most intracellular proteins. It regulates numerous cellular processes, including the removal of misfolded or unfolded proteins, cell cycle control, and regulation of apoptosis. However, the function of proteasome subunits in viral immunity has not been well characterized. In this study, we identified PSMB1, a member of the proteasome β subunits (PSMB) family, as a negative regulator of innate immune responses during viral infection. Knockdown of PSMB1 enhanced the RNA virus-induced cytokine and chemokine production. Overexpression of PSMB1 abolished virus-induced activation of the interferon-stimulated response element (ISRE) and interferon beta (IFNβ) promoters. Mechanistically, PSMB1 inhibited the activation of RIG-I-like receptor (RLR) and Toll-like receptor 3 (TLR3) signaling pathways. PSMB1 was induced after viral infection and its interaction with IKK-ε promoted degradation of IKK-ε through the ubiquitin-proteasome system. Collectively, our study demonstrates PSMB1 is an important regulator of innate immune signaling.

KEYWORDS:

IKK-ε; PSMB1; RIG-I; TLR3; cytokine; innate immunity

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