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Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy
- Source :
- Nature communications. 13(1)
- Publication Year :
- 2021
-
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.
- Subjects :
- Multidisciplinary
SARS-CoV-2
Ubiquitin-Protein Ligases
Intracellular Signaling Peptides and Proteins
General Physics and Astronomy
COVID-19
Sumoylation
General Chemistry
General Biochemistry, Genetics and Molecular Biology
Cysteine Endopeptidases
Spike Glycoprotein, Coronavirus
Autophagy
Humans
Angiotensin-Converting Enzyme 2
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....f0b35f810a07ebe7148484a14076ab66