Suppression of ACE2 SUMOylation Protects Against SARS-CoV-2 Infection Through TOLLIP-mediated Selective Autophagy

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 3

PMID 36057605

Authors

Shouheng Jin

Xing He

Ling Ma

Zhen Zhuang

Yiliang Wang

Meng Lin

Sihui Cai

Lu Wei

Zheyu Wang

Zhiyao Zhao

Yaoxing Wu

Lin Sun

Chunwei Li

Weihong Xie

Yong Zhao

Zhou Songyang

Ke Peng

Jincun Zhao

Jun Cui

Affiliations

Soon will be listed here.

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.

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