IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32957-y.html
   My bibliography  Save this article

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

Author

Listed:
  • Shouheng Jin

    (Sun Yat-sen University)

  • Xing He

    (Sun Yat-sen University)

  • Ling Ma

    (Sun Yat-sen University)

  • Zhen Zhuang

    (The First Affiliated Hospital of Guangzhou Medical University)

  • Yiliang Wang

    (The First Affiliated Hospital of Guangzhou Medical University)

  • Meng Lin

    (Sun Yat-sen University)

  • Sihui Cai

    (Sun Yat-sen University)

  • Lu Wei

    (Sun Yat-sen University)

  • Zheyu Wang

    (Sun Yat-sen University)

  • Zhiyao Zhao

    (The First Affiliated Hospital of Guangzhou Medical University)

  • Yaoxing Wu

    (Sun Yat-sen University)

  • Lin Sun

    (Sun Yat-sen University)

  • Chunwei Li

    (Sun Yat-sen University)

  • Weihong Xie

    (Sun Yat-sen University)

  • Yong Zhao

    (Sun Yat-sen University)

  • Zhou Songyang

    (Sun Yat-sen University)

  • Ke Peng

    (Chinese Academy of Sciences)

  • Jincun Zhao

    (The First Affiliated Hospital of Guangzhou Medical University)

  • Jun Cui

    (Sun Yat-sen University)

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.

Suggested Citation

  • 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 &, 2022. "Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32957-y
    DOI: 10.1038/s41467-022-32957-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32957-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32957-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chongyang Li & Francis P. McManus & Cédric Plutoni & Cristina Mirela Pascariu & Trent Nelson & Lara Elis Alberici Delsin & Gregory Emery & Pierre Thibault, 2020. "Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Jian Shang & Gang Ye & Ke Shi & Yushun Wan & Chuming Luo & Hideki Aihara & Qibin Geng & Ashley Auerbach & Fang Li, 2020. "Structural basis of receptor recognition by SARS-CoV-2," Nature, Nature, vol. 581(7807), pages 221-224, May.
    3. Nils C. Gassen & Jan Papies & Thomas Bajaj & Jackson Emanuel & Frederik Dethloff & Robert Lorenz Chua & Jakob Trimpert & Nicolas Heinemann & Christine Niemeyer & Friderike Weege & Katja Hönzke & Tom A, 2021. "SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    4. Wenhui Li & Michael J. Moore & Natalya Vasilieva & Jianhua Sui & Swee Kee Wong & Michael A. Berne & Mohan Somasundaran & John L. Sullivan & Katherine Luzuriaga & Thomas C. Greenough & Hyeryun Choe & M, 2003. "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus," Nature, Nature, vol. 426(6965), pages 450-454, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Fabian Zech & Daniel Schniertshauer & Christoph Jung & Alexandra Herrmann & Arne Cordsmeier & Qinya Xie & Rayhane Nchioua & Caterina Prelli Bozzo & Meta Volcic & Lennart Koepke & Janis A. Müller & Jan, 2021. "Spike residue 403 affects binding of coronavirus spikes to human ACE2," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Milad Haghani & Pegah Varamini, 2021. "Temporal evolution, most influential studies and sleeping beauties of the coronavirus literature," Scientometrics, Springer;Akadémiai Kiadó, vol. 126(8), pages 7005-7050, August.
    5. Mohamed A. Farrag & Haitham M. Amer & Rauf Bhat & Maaweya E. Hamed & Ibrahim M. Aziz & Ayman Mubarak & Turki M Dawoud & Sami G Almalki & Fayez Alghofaili & Ahmad K. Alnemare & Raid Saleem Al-Baradi & , 2021. "SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis," IJERPH, MDPI, vol. 18(12), pages 1-14, June.
    6. Behrooz Darbani, 2020. "The Expression and Polymorphism of Entry Machinery for COVID-19 in Human: Juxtaposing Population Groups, Gender, and Different Tissues," IJERPH, MDPI, vol. 17(10), pages 1-8, May.
    7. Byung Uk Lee, 2021. "Why Does the SARS-CoV-2 Delta VOC Spread So Rapidly? Universal Conditions for the Rapid Spread of Respiratory Viruses, Minimum Viral Loads for Viral Aerosol Generation, Effects of Vaccination on Viral," IJERPH, MDPI, vol. 18(18), pages 1-6, September.
    8. David Gomez-Zepeda & Danielle Arnold-Schild & Julian Beyrle & Arthur Declercq & Ralf Gabriels & Elena Kumm & Annica Preikschat & Mateusz Krzysztof Łącki & Aurélie Hirschler & Jeewan Babu Rijal & Chris, 2024. "Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS2Rescore with MS2PIP timsTOF fragmentation prediction model," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    9. Indrikis A. Krams & Priit Jõers & Severi Luoto & Giedrius Trakimas & Vilnis Lietuvietis & Ronalds Krams & Irena Kaminska & Markus J. Rantala & Tatjana Krama, 2021. "The Obesity Paradox Predicts the Second Wave of COVID-19 to Be Severe in Western Countries," IJERPH, MDPI, vol. 18(3), pages 1-10, January.
    10. Oskar Staufer & Kapil Gupta & Jochen Estebano Hernandez Bücher & Fabian Kohler & Christian Sigl & Gunjita Singh & Kate Vasileiou & Ana Yagüe Relimpio & Meline Macher & Sebastian Fabritz & Hendrik Diet, 2022. "Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Diego Fernández-Lázaro & Jerónimo J. González-Bernal & Nerea Sánchez-Serrano & Lourdes Jiménez Navascués & Ana Ascaso-del-Río & Juan Mielgo-Ayuso, 2020. "Physical Exercise as a Multimodal Tool for COVID-19: Could It Be Used as a Preventive Strategy?," IJERPH, MDPI, vol. 17(22), pages 1-13, November.
    12. Marysia Wrona & Damian Skrypnik, 2022. "New-Onset Diabetes Mellitus, Hypertension, Dyslipidaemia as Sequelae of COVID-19 Infection—Systematic Review," IJERPH, MDPI, vol. 19(20), pages 1-10, October.
    13. Peter Radvak & Hyung-Joon Kwon & Martina Kosikova & Uriel Ortega-Rodriguez & Ruoxuan Xiang & Je-Nie Phue & Rong-Fong Shen & James Rozzelle & Neeraj Kapoor & Taylor Rabara & Jeff Fairman & Hang Xie, 2021. "SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    14. Nagla A. El-Shitany & Manal El-Hamamsy & Ahlam A. Alahmadi & Basma G. Eid & Thikryat Neamatallah & Haifa S. Almukadi & Rana A. Arab & Khadija A. Faddladdeen & Khayria A. Al-Sulami & Safia M. Bahshwan , 2021. "The Impact of ABO Blood Grouping on COVID-19 Vulnerability and Seriousness: A Retrospective Cross-Sectional Controlled Study among the Arab Community," IJERPH, MDPI, vol. 18(1), pages 1-19, January.
    15. Ma’ayan Israeli & Yaara Finkel & Yfat Yahalom-Ronen & Nir Paran & Theodor Chitlaru & Ofir Israeli & Inbar Cohen-Gihon & Moshe Aftalion & Reut Falach & Shahar Rotem & Uri Elia & Ital Nemet & Limor Klik, 2022. "Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    16. Xuanming Guo & Jianli Cao & Jian-Piao Cai & Jiayan Wu & Jiangang Huang & Pallavi Asthana & Sheung Kin Ken Wong & Zi-Wei Ye & Susma Gurung & Yijing Zhang & Sheng Wang & Zening Wang & Xin Ge & Hiu Yee K, 2022. "Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Cedric C. S. Tan & Su Datt Lam & Damien Richard & Christopher J. Owen & Dorothea Berchtold & Christine Orengo & Meera Surendran Nair & Suresh V. Kuchipudi & Vivek Kapur & Lucy van Dorp & François Ball, 2022. "Transmission of SARS-CoV-2 from humans to animals and potential host adaptation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Charulata Jindal & Sandeep Kumar & Sunil Sharma & Yuk Ming Choi & Jimmy T. Efird, 2020. "The Prevention and Management of COVID-19: Seeking a Practical and Timely Solution," IJERPH, MDPI, vol. 17(11), pages 1-11, June.
    19. Tomasz Gęca & Kamila Wojtowicz & Paweł Guzik & Tomasz Góra, 2022. "Increased Risk of COVID-19 in Patients with Diabetes Mellitus—Current Challenges in Pathophysiology, Treatment and Prevention," IJERPH, MDPI, vol. 19(11), pages 1-17, May.
    20. Qizhou Lian & Kui Zhang & Zhao Zhang & Fuyu Duan & Liyan Guo & Weiren Luo & Bobo Wing-Yee Mok & Abhimanyu Thakur & Xiaoshan Ke & Pedram Motallebnejad & Vlad Nicolaescu & Jonathan Chen & Chui Yan Ma & , 2022. "Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32957-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.