Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells / 医学前沿
Frontiers of Medicine
; (4): 252-263, 2021.
Article
in En
| WPRIM
| ID: wpr-880970
Responsible library:
WPRO
ABSTRACT
An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Key words
Full text:
1
Database:
WPRIM
Main subject:
Peptidyl-Dipeptidase A
/
Ubiquitin-Protein Ligases
/
Epithelial Cells
/
Pandemics
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
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COVID-19
/
Lung
Limits:
Animals
/
Humans
Language:
En
Journal:
Frontiers of Medicine
Year:
2021
Document type:
Article