Sökning: WFRF:(Lindskog A.) >
Mechanistic insight...
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Pablos, IsabelUniv 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.
(författare)
Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome
- Artikel/kapitelEngelska2021
Förlag, utgivningsår, omfång ...
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Cell Press,2021
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-459079
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-459079URI
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https://doi.org/10.1016/j.celrep.2021.109892DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:147992902URI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Machado, YoanUniv 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.
(författare)
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de Jesus, Hugo C. RamosUniv 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.
(författare)
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Mohamud, YasirUniv British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC V6Z 1Y6, Canada.
(författare)
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Kappelhoff, ReinhildUniv 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.
(författare)
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Lindskog, CeciliaUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi(Swepub:uu)cecli129
(författare)
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Vlok, MarliUniv British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Life Sci Inst, Vancouver, BC V6T 1Z3, Canada.
(författare)
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Bell, Peter A.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.
(författare)
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Butler, Georgina S.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.
(författare)
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Grin, Peter M.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.
(författare)
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Cao, Quynh T.McMaster Univ, Fac Hlth Sci, Firestone Inst Resp Hlth, Hamilton, ON L8N 4A6, Canada.
(författare)
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Nguyen, Jenny P.McMaster Univ, Fac Hlth Sci, Firestone Inst Resp Hlth, Hamilton, ON L8N 4A6, Canada.
(författare)
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Solis, NestorUniv 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.
(författare)
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Abbina, SrinivasUniv 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.
(författare)
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Rut, WiolettaWroclaw Univ Sci & Technol, Dept Chem Biol & Bioimaging, Wyb Wyspianskiego 27, PL-50370 Wroclaw, Poland.
(författare)
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Vederas, John C.Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada.
(författare)
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Szekely, LaszloKarolinska Institutet
(författare)
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Szakos, AttilaKarolinska Univ Labs, Dept Clin Pathol & Canc Diagnost, S-14186 Stockholm, Sweden.
(författare)
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Drag, MarcinWroclaw Univ Sci & Technol, Dept Chem Biol & Bioimaging, Wyb Wyspianskiego 27, PL-50370 Wroclaw, Poland.
(författare)
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Kizhakkedathu, Jayachandran N.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.
(författare)
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Mossman, KarenMcMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada.
(författare)
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Hirota, Jeremy A.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.
(författare)
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Jan, EricUniv British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.;Univ British Columbia, Life Sci Inst, Vancouver, BC V6T 1Z3, Canada.
(författare)
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Luo, HonglinUniv British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada.;St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC V6Z 1Y6, Canada.
(författare)
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Banerjee, ArinjayMcMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada.;Univ Saskatchewan, Dept Vet Microbiol, Vaccine & Infect Dis Org, Saskatoon, SK S7N 5E3, Canada.
(författare)
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Overall, Christopher M.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.
(författare)
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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)
Sammanhörande titlar
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Ingår i:Cell Reports: Cell Press37:42211-1247
Internetlänk
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Till lärosätets databas
- 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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visa färre...
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Cell Reports
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Uppsala universitet
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Karolinska Institutet