A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis
Abstract
The N-end rule pathway is an evolutionarily conserved proteolytic system that degrades proteins containing N-terminal degradation signals called N-degrons, and has emerged as a key regulator of various processes. Viruses manipulate diverse host pathways to facilitate viral replication and evade antiviral defenses. However, it remains unclear if viral infection has any impact on the N-end rule pathway. Here, using a picorna-like virus as a model, we found that viral infection promoted the accumulation of caspase-cleaved Drosophila Inhibitor of Apoptosis 1 (DIAP1) by inducing the degradation of N-terminal amidohydrolase 1 (NTAN1), a key N-end rule component that identifies N-degron to initiate the process. The virus-induced NTAN1 degradation is independent of polyubiquitylation but dependent on proteasome. Furthermore, the virus-induced N-end rule pathway suppression inhibits apoptosis and benefits viral replication. Thus, our findings demonstrate that a virus can suppress the N-end rule pathway, and uncover a new mechanism for virus to evade apoptosis.
Article and author information
Author details
Funding
National Natural Science Foundation of China (No. 31522004)
- Xi Zhou
National Natural Science Foundation of China (No. 31600126)
- Zhaowei Wang
Academy of Medical Sciences (No. 31761130075)
- Xi Zhou
National Basic Research Program of China (No. 2014CB542603)
- Xi Zhou
National High-Tech R&D Program of China (No. 2015AA020939)
- Xi Zhou
Strategic Priority Research Program of Chinese Academy of Sciences (No. XDPB0301)
- Xi Zhou
Natural Science Foundation of Hubei Province (No. 2016CFA045)
- Xi Zhou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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