tetano
Editor, Senior Moderator
Nat Commun
. 2022 Sep 3;13(1):5204.
doi: 10.1038/s41467-022-32957-y.
Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy
Shouheng Jin[SUP] #[/SUP][SUP] 1 [/SUP], Xing He[SUP] #[/SUP][SUP] 2 [/SUP], Ling Ma[SUP] 2 [/SUP], Zhen Zhuang[SUP] 3 [/SUP], Yiliang Wang[SUP] 3 [/SUP], Meng Lin[SUP] 2 [/SUP], Sihui Cai[SUP] 2 [/SUP], Lu Wei[SUP] 2 [/SUP], Zheyu Wang[SUP] 2 [/SUP], Zhiyao Zhao[SUP] 3 [/SUP], Yaoxing Wu[SUP] 2 [/SUP], Lin Sun[SUP] 4 [/SUP], Chunwei Li[SUP] 4 [/SUP], Weihong Xie[SUP] 2 [/SUP], Yong Zhao[SUP] 2 [/SUP], Zhou Songyang[SUP] 2 [/SUP], Ke Peng[SUP] 5 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Jun Cui[SUP] 6 [/SUP]
Affiliations
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.
. 2022 Sep 3;13(1):5204.
doi: 10.1038/s41467-022-32957-y.
Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy
Shouheng Jin[SUP] #[/SUP][SUP] 1 [/SUP], Xing He[SUP] #[/SUP][SUP] 2 [/SUP], Ling Ma[SUP] 2 [/SUP], Zhen Zhuang[SUP] 3 [/SUP], Yiliang Wang[SUP] 3 [/SUP], Meng Lin[SUP] 2 [/SUP], Sihui Cai[SUP] 2 [/SUP], Lu Wei[SUP] 2 [/SUP], Zheyu Wang[SUP] 2 [/SUP], Zhiyao Zhao[SUP] 3 [/SUP], Yaoxing Wu[SUP] 2 [/SUP], Lin Sun[SUP] 4 [/SUP], Chunwei Li[SUP] 4 [/SUP], Weihong Xie[SUP] 2 [/SUP], Yong Zhao[SUP] 2 [/SUP], Zhou Songyang[SUP] 2 [/SUP], Ke Peng[SUP] 5 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Jun Cui[SUP] 6 [/SUP]
Affiliations
- 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.