| Title: |
Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication |
| Authors: |
Yaron, Tomer M; Heaton, Brook E; Levy, Tyler M; Johnson, Jared L; Jordan, Tristan X; Cohen, Benjamin M; Kerelsky, Alexander; Lin, Ting-Yu; Liberatore, Katarina M; Bulaon, Danielle K; Van Nest, Samantha J; Koundouros, Nikos; Kastenhuber, Edward R; Mercadante, Marisa N; Shobana-Ganesh, Kripa; He, Long; Schwartz, Robert E; Chen, Shuibing; Weinstein, Harel; Elemento, Olivier; Piskounova, Elena; Nilsson-Payant, Benjamin E; Lee, Gina; Trimarco, Joseph D; Burke, Kaitlyn N; Hamele, Cait E; Chaparian, Ryan R; Harding, Alfred T; Tata, Aleksandra; Zhu, Xinyu; Tata, Purushothama Rao; Smith, Clare M; Possemato, Anthony P; Tkachev, Sasha L; Hornbeck, Peter V; Beausoleil, Sean A; Anand, Shankara K; Aguet, François; Getz, Gad; Davidson, Andrew D; Heesom, Kate; Kavanagh-Williamson, Maia; Matthews, David A; tenOever, Benjamin R; Cantley, Lewis C; Blenis, John; Heaton, Nicholas S |
| Source: |
Science Signaling, vol 15, iss 757 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2022 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
3101 Biochemistry and Cell Biology (for-2020); 31 Biological Sciences (for-2020); Coronaviruses (rcdc); Emerging Infectious Diseases (rcdc); Infectious Diseases (rcdc); 2.2 Factors relating to the physical environment (hrcs-rac); Infection (hrcs-hc); 3 Good Health and Well Being (sdg); Animals (mesh); Humans (mesh); SARS-CoV-2 (mesh); Phosphorylation (mesh); COVID-19 (mesh); Glycogen Synthase Kinase 3 (mesh); Virus Replication (mesh); Nucleocapsid Proteins (mesh); Nucleocapsid (mesh); Serine (mesh); Threonine (mesh); Mammals (mesh); Protein Serine-Threonine Kinases (mesh); 0601 Biochemistry and Cell Biology (for) |
| Subject Geographic: |
eabm0808 - eabm0808 |
| Description: |
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt44d513nc; https://escholarship.org/uc/item/44d513nc; https://escholarship.org/content/qt44d513nc/qt44d513nc.pdf |
| DOI: |
10.1126/scisignal.abm0808 |
| Availability: |
https://escholarship.org/uc/item/44d513nc; https://escholarship.org/content/qt44d513nc/qt44d513nc.pdf; https://doi.org/10.1126/scisignal.abm0808 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.C4867259 |
| Database: |
BASE |