Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells.
10.1007/s11684-021-0837-6
- Author:
Guizhen WANG
1
;
Qun ZHAO
1
;
Hui ZHANG
2
;
Fan LIANG
1
;
Chen ZHANG
1
;
Jun WANG
3
;
Zhenyin CHEN
1
;
Ran WU
1
;
Hong YU
4
;
Beibei SUN
1
;
Hua GUO
1
;
Ruie FENG
2
;
Kaifeng XU
3
;
Guangbiao ZHOU
5
Author Information
1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
3. Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
4. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
5. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. gbzhou@cicams.ac.cn.
- Publication Type:Journal Article
- Keywords:
ACE2;
SARS-CoV-2;
Skp2;
benzo(a)pyrene;
tobacco smoke
- MeSH:
Adult;
Animals;
COVID-19;
Epithelial Cells;
Humans;
Lung;
Mice;
Pandemics;
Peptidyl-Dipeptidase A;
SARS-CoV-2;
Spike Glycoprotein, Coronavirus;
Ubiquitin-Protein Ligases/genetics*
- From:
Frontiers of Medicine
2021;15(2):252-263
- CountryChina
- Language:English
-
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.
