Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein.
Biochem Biophys Res Commun
; 529(2): 251-256, 2020 08 20.
Artículo
en Inglés
| 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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Neumonía Viral
/
Autoantígenos
/
Infecciones por Coronavirus
/
Proteínas de la Nucleocápside
/
Complejo de la Endopetidasa Proteasomal
/
Proteolisis
/
Betacoronavirus
Límite:
Humanos
Idioma:
Inglés
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Artículo
País de afiliación:
J.bbrc.2020.06.058
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