Virology & Mycology
Open Access
ISSN: 2161-0517
+44 1223 790975
ISSN: 2161-0517
+44 1223 790975
Zhaocai Zhou, Qian Hao, Shi Jiao, Zhubing Shi, Chuanchuan Li, Xia Meng, Zhen Zhang, Yanyan Wang, Xiaomin Song, Wenjia Wang, Rongguang Zhang, Yun Zhao and Catherine CL Wong
Chinese Academy of Sciences, China
Scientific Tracks Abstracts: Virol-mycol
RIG-I is a well-studied sensor of viral RNA that plays a key role in innate immunity. p97 regulates a variety of cellular events such as protein quality control, membrane reassembly, DNA repair, and the cell cycle. Here, we report a new role for p97 with Npl4- Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181. Viral infection significantly strengthens the interaction between RIG-I and the p97 complex by a conformational change of RIG-I that exposes the CARDs and through K63-linked ubiquitination of these CARDs. Disruption of the p97 complex enhances RIG-I antiviral signaling. Consistently, administration of compounds targeting p97 ATPase activity was shown to inhibit viral replication and protect mice from vesicular stomatitis virus (VSV) infection. Overall, our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97 complex as a potential drug target in antiviral therapy.
Zhaocai Zhou obtained his PhD degree from University of Science and Technology of China, 2004; and received his Post-doctoral training from Brandeis University, and University of Pennsylvania, USA, 2004–2008. He joined the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in 2009, and became a Professor of ShanghaiTech University in 2015. His primary research interest is in understanding the signaling mechanism of tumorigenesis and tumor-related immune regulation. His recent work focuses on Hippo/MST signaling pathway and macrophage plasticity.
Email: zczhou@sibcb.ac.cn