Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells

被引：30

作者：

Wang, Guizhen ^{[1
,2
,3
]}

Zhao, Qun ^{[1
,4
]}

Zhang, Hui ^{[5
]}

Liang, Fan ^{[1
,2
,3
]}

Zhang, Chen ^{[1
,2
,3
]}

Wang, Jun ^{[6
]}

Chen, Zhenyin ^{[1
,7
]}

Wu, Ran ^{[1
,7
]}

Yu, Hong ^{[8
]}

Sun, Beibei ^{[1
]}

Guo, Hua ^{[1
]}

Feng, Ruie ^{[5
]}

Xu, Kaifeng ^{[6
]}

Zhou, Guangbiao ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc, Natl Canc Ctr,Canc Hosp, Beijing 100021, Peoples R China

[2] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100101, Peoples R China

[4] Hubei Univ Med, Shiyan 442000, Peoples R China

[5] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Pathol, Beijing 100730, Peoples R China

[6] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Pulm & Crit Care Med, Beijing 100730, Peoples R China

[7] Guizhou Univ, Sch Med, Guiyang 550025, Peoples R China

[8] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China

来源：

FRONTIERS OF MEDICINE | 2021年 / 15卷 / 02期

基金：

中国国家自然科学基金; 国家杰出青年科学基金;

关键词：

SARS-CoV-2; tobacco smoke; benzo(a)pyrene; ACE2; Skp2; ARYL-HYDROCARBON RECEPTOR; TOBACCO; EXPRESSION; ENTRY;

D O I：

10.1007/s11684-021-0837-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：252 / 263

页数：12

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