Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein.
Biochem Biophys Res Commun
; 529(2): 251-256, 2020 08 20.
Article
in English
| MEDLINE | ID: covidwho-1220683
ABSTRACT
The nucleocapsid protein is significant in the formation of viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounting for the largest proportion of viral structural proteins. Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28γ as a nCoV N binding protein by co-immunoprecipitation assay. As a result of their interaction, nCoV N could be degraded by PA28γ-20S in vitro degradation assay. This was also demonstrated by blocking de novo protein synthesis with cycloheximide. The stability of nCoV N in PA28γ-knockout cells was greater than in PA28γ-wildtype cells. Notably, immunofluorescence staining revealed that knockout of the PA28γ gene in cells led to the transport of nCoV N from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced proteolysis of nCoV N compared to that in PA28γ-N151Y cells containing a dominant-negative PA28γ mutation, which reduced this process. These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Autoantigens
/
Coronavirus Infections
/
Nucleocapsid Proteins
/
Proteasome Endopeptidase Complex
/
Proteolysis
/
Betacoronavirus
Limits:
Humans
Language:
English
Journal:
Biochem Biophys Res Commun
Year:
2020
Document Type:
Article
Affiliation country:
J.bbrc.2020.06.058
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