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10.1016/j.bbrc.2020.06.058

http://scihub22266oqcxt.onion/10.1016/j.bbrc.2020.06.058
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32703419!7296323!32703419
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suck abstract from ncbi


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pmid32703419      Biochem+Biophys+Res+Commun 2020 ; 529 (2): 251-256
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  • Proteasome activator PA28gamma-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein #MMPMID32703419
  • Zhang H; Tu J; Cao C; Yang T; Gao L
  • Biochem Biophys Res Commun 2020[Aug]; 529 (2): 251-256 PMID32703419show ga
  • 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 PA28gamma regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28gamma as a nCoV N binding protein by co-immunoprecipitation assay. As a result of their interaction, nCoV N could be degraded by PA28gamma-20S in vitro degradation assay. This was also demonstrated by blocking de novo protein synthesis with cycloheximide. The stability of nCoV N in PA28gamma-knockout cells was greater than in PA28gamma-wildtype cells. Notably, immunofluorescence staining revealed that knockout of the PA28gamma gene in cells led to the transport of nCoV N from the nucleus to the cytoplasm. Overexpression of PA28gamma enhanced proteolysis of nCoV N compared to that in PA28gamma-N151Y cells containing a dominant-negative PA28gamma mutation, which reduced this process. These results suggest that PA28gamma 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.
  • |*Proteolysis[MESH]
  • |Autoantigens/*metabolism[MESH]
  • |Betacoronavirus/*metabolism[MESH]
  • |COVID-19[MESH]
  • |Coronavirus Infections/*metabolism/virology[MESH]
  • |Coronavirus Nucleocapsid Proteins[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |In Vitro Techniques[MESH]
  • |Nucleocapsid Proteins/*metabolism[MESH]
  • |Pandemics[MESH]
  • |Phosphoproteins[MESH]
  • |Pneumonia, Viral/*metabolism/virology[MESH]
  • |Proteasome Endopeptidase Complex/*metabolism[MESH]
  • |Protein Binding[MESH]
  • |Protein Stability[MESH]
  • |Protein Transport[MESH]


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