2. Academic Validation
  3. Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy

Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy

  • Nat Commun. 2022 Sep 3;13(1):5204. doi: 10.1038/s41467-022-32957-y.
Shouheng Jin  # 1,  Xing He  # 2,  Ling Ma 2,  Zhen Zhuang 3,  Yiliang Wang 3,  Meng Lin 2,  Sihui Cai 2,  Lu Wei 2,  Zheyu Wang 2,  Zhiyao Zhao 3,  Yaoxing Wu 2,  Lin Sun 4,  Chunwei Li 4,  Weihong Xie 2,  Yong Zhao 2,  Zhou Songyang 2,  Ke Peng 5,  Jincun Zhao 3,  Jun Cui 6
Affiliations

Affiliations

  • 1 Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, 510275, Guangzhou, Guangdong, China. jinshh3@mail.sysu.edu.cn.
  • 2 Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, 510275, Guangzhou, Guangdong, China.
  • 3 State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, 510182, Guangzhou, Guangdong, China.
  • 4 Department of Otolaryngology, First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • 5 State Key Laboratory of Virology, CAS Key Laboratory of Special Pathogens, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071, Wuhan, Hubei, China.
  • 6 Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, 510275, Guangzhou, Guangdong, China. cuij5@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 36057605 DOI: 10.1038/s41467-022-32957-y
Abstract

In addition to investigating the virology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovering the host-virus dependencies are essential to identify and design effective Antiviral therapy strategy. Here, we report that the SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) and provide evidence indicating that prevention of ACE2 SUMOylation can block SARS-CoV-2 Infection. E3 SUMO Ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation Enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. TOLLIP deficiency results in the stabilization of ACE2 and elevated SARS-CoV-2 Infection. In conclusion, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination as a potential way to combat SARS-CoV-2 Infection.

Figures
Products