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Mechanistic insight...
Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome
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- Pablos, Isabel (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.
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- Machado, Yoan (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.
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- de Jesus, Hugo C. Ramos (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.
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visa fler...
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- Mohamud, Yasir (författare)
- Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC V6Z 1Y6, Canada.
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- Kappelhoff, Reinhild (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.
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- Lindskog, Cecilia (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi
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- Vlok, Marli (författare)
- Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Life Sci Inst, Vancouver, BC V6T 1Z3, Canada.
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- Bell, Peter A. (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.
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- Butler, Georgina S. (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.
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- Grin, Peter M. (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
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- Cao, Quynh T. (författare)
- McMaster Univ, Fac Hlth Sci, Firestone Inst Resp Hlth, Hamilton, ON L8N 4A6, Canada.
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- Nguyen, Jenny P. (författare)
- McMaster Univ, Fac Hlth Sci, Firestone Inst Resp Hlth, Hamilton, ON L8N 4A6, Canada.
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- Solis, Nestor (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.;AbCellera Biol Inc, Vancouver, BC V5Y 0A1, Canada.
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- Abbina, Srinivas (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;Univ British Columbia, Sch Biomed Engn, Vancouver, BC V6T 1Z3, Canada.;Precis NanoSyst, Vancouver, BC V6P 6T7, Canada.
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- Rut, Wioletta (författare)
- Wroclaw Univ Sci & Technol, Dept Chem Biol & Bioimaging, Wyb Wyspianskiego 27, PL-50370 Wroclaw, Poland.
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- Vederas, John C. (författare)
- Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada.
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- Szekely, Laszlo (författare)
- Karolinska Institutet
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- Szakos, Attila (författare)
- Karolinska Univ Labs, Dept Clin Pathol & Canc Diagnost, S-14186 Stockholm, Sweden.
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- Drag, Marcin (författare)
- Wroclaw Univ Sci & Technol, Dept Chem Biol & Bioimaging, Wyb Wyspianskiego 27, PL-50370 Wroclaw, Poland.
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- Kizhakkedathu, Jayachandran N. (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;Univ British Columbia, Sch Biomed Engn, Vancouver, BC V6T 1Z3, Canada.
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- Mossman, Karen (författare)
- McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada.
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- Hirota, Jeremy A. (författare)
- McMaster Univ, Fac Hlth Sci, Firestone Inst Resp Hlth, Hamilton, ON L8N 4A6, Canada.;McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada.;Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada.;Univ British Columbia, Dept Med, Div Resp Med, Vancouver, BC V6T 1Z3, Canada.
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- Jan, Eric (författare)
- Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Life Sci Inst, Vancouver, BC V6T 1Z3, Canada.
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- Luo, Honglin (författare)
- Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC V6Z 1Y6, Canada.
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- Banerjee, Arinjay (författare)
- McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada.;Univ Saskatchewan, Dept Vet Microbiol, Vaccine & Infect Dis Org, Saskatoon, SK S7N 5E3, Canada.
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- Overall, Christopher M. (författare)
- Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
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Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC V6Z 1Y6, Canada. (creator_code:org_t)
- Cell Press, 2021
- 2021
- Engelska.
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Ingår i: Cell Reports. - : Cell Press. - 2211-1247. ; 37:4
- Relaterad länk:
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https://doi.org/10.1...
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visa fler...
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https://uu.diva-port... (primary) (Raw object)
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The main viral protease (3CL(pro)) is indispensable for SARS-CoV-2 replication. We delineate the human protein substrate landscape of 3CL(pro) by TAILS substrate-targeted N-terminomics. We identify more than 100 substrates in human lung and kidney cells supported by analyses of SARS-CoV-2-infected cells. Enzyme kinetics and molecular docking simulations of 3CL(pro) engaging substrates reveal how noncanonical cleavage sites, which diverge from SARS-CoV, guide substrate specificity. Cleaving the interactors of essential effector proteins, effectively stranding them from their binding partners, amplifies the consequences of proteolysis. We show that 3CL(pro) targets the Hippo pathway, including inactivation of MAP4K5, and key effectors of transcription, mRNA processing, and translation. We demonstrate that Spike glycoprotein directly binds galectin-8, with galectin-8 cleavage disengaging CALCOCO2/NDP52 to decouple antiviral-autophagy. Indeed, in post-mortem COVID-19 lung samples, NDP52 rarely colocalizes with galectin-8, unlike in healthy lungs. The 3CL(pro) substrate degradome establishes a foundational substrate atlas to accelerate exploration of SARSCoV-2 pathology and drug design.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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- Av författaren/redakt...
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Pablos, Isabel
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Machado, Yoan
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de Jesus, Hugo C ...
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Mohamud, Yasir
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Kappelhoff, Rein ...
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Lindskog, Cecili ...
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visa fler...
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Vlok, Marli
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Bell, Peter A.
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Butler, Georgina ...
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Grin, Peter M.
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Cao, Quynh T.
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Nguyen, Jenny P.
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Solis, Nestor
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Abbina, Srinivas
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Rut, Wioletta
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Vederas, John C.
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Szekely, Laszlo
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Szakos, Attila
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Drag, Marcin
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Kizhakkedathu, J ...
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Mossman, Karen
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Hirota, Jeremy A ...
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Jan, Eric
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Luo, Honglin
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Banerjee, Arinja ...
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Overall, Christo ...
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- MEDICIN OCH HÄLSOVETENSKAP
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Cell Reports
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet