ArticleThe Journal of biological chemistry2009
Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 217 citations in OpenAlex.
- Nsp3 Ubl1-orchestrated dephosphorylation of N protein promotes coronaviral subgenomic RNA synthesis.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 membrane protein recruits PP2A to dephosphorylate the nucleocapsid and promote virion production.Journal of biomedical science · 2026Article
- SARS-CoV-2 nonstructural protein 3 remodels the phosphorylation of target proteins via protein-protein interactions.Microbiology spectrum · 2026Article
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- Coronavirus genome packaging and nucleocapsid assembly.Journal of virology · 2026Review
- Mechanism of SARS-CoV-2 Nucleocapsid Protein Phosphorylation-Induced Functional Switch.Viruses · 2026Article
- Intramolecular loops control SARS-CoV-2 nucleocapsid protein self-association and nucleic acid binding dependent on phosphorylation.bioRxiv : the preprint server for biology · 2026Article
- Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.Hepatology (Baltimore, Md.) · 2025Article
- Characterization of the binding features between SARS-CoV-2 5'-proximal transcripts of genomic RNA and nucleocapsid proteins.RNA biology · 2025Review
- Glycogen synthase kinase 3 promotes the proliferation of porcine epidemic diarrhoea virus by phosphorylating the nucleocapsid protein.Virulence · 2025Article
- Phosphorylation Changes SARS-CoV-2 Nucleocapsid Protein's Structural Dynamics and Its Interaction With RNA.Proteins · 2025Article
- JNK kinase regulates phosphorylation of HCoV-229E nucleocapsid protein.Npj viruses · 2025Article
- GSK3A promotes human adenovirus replication and phosphorylates viral L4-22K protein.Life science alliance · 2025Article
- Phosphorylation toggles the SARS-CoV-2 nucleocapsid protein between two membrane-associated condensate states.Nature communications · 2025Article
- Mutations differentially affecting the coronavirus Mac1 ADP-ribose binding and hydrolysis activities indicate that it promotes multiple stages of the viral replication cycle.Journal of virology · 2025Article
- Anti-Influenza Activity of 6BIGOE: Improved Pharmacological Profile After Encapsulation in PLGA Nanoparticles.International journal of molecular sciences · 2025Article
- Tradeoffs between proliferation and transmission in virus evolution- insights from evolutionary and functional analyses of SARS-CoV-2.Virology journal · 2025Article
- Variant mutation G215C in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.PLoS biology · 2025Article
- Phosphorylation Modifications and Their Role in Viral Pneumonia: Mechanisms and Therapeutic Implications.Infection and drug resistance · 2025Review
- Spatiotemporal protein interactome profiling through condensation-enhanced photocrosslinking.Nature chemistry · 2025Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronavirus (CoV) nucleocapsid (N) protein is a highly phosphorylated protein required for viral replication, but whether its phosphorylation and the related kinases are involved in the viral life cycle is unknown. We found the severe acute respiratory syndrome CoV N protein to be an appropriate system to address this issue. Using high resolution PAGE analysis, this protein could be separated into phosphorylated and unphosphorylated isoforms. Mass spectrometric analysis and deletion mapping showed that the major phosphorylation sites were located at the central serine-arginine (SR)-rich motif that contains several glycogen synthase kinase (GSK)-3 substrate consensus sequences. GSK-3-specific inhibitor treatment dephosphorylated the N protein, and this could be recovered by the constitutively active GSK-3 kinase. Immunoprecipitation brought down both N and GSK-3 proteins in the same complex, and the N protein could be phosphorylated directly at its SR-rich motif by GSK-3 using an in vitro kinase assay. Mutation of the two priming sites critical for GSK-3 phosphorylation in the SR-rich motif abolished N protein phosphorylation. Finally, GSK-3 inhibitor was found to reduce N phosphorylation in the severe acute respiratory syndrome CoV-infected VeroE6 cells and decrease the viral titer and cytopathic effects. The effect of GSK-3 inhibitor was reproduced in another coronavirus, the neurotropic JHM strain of mouse hepatitis virus. Our results indicate that GSK-3 is critical for CoV N protein phosphorylation and suggest that it plays a role in regulating the viral life cycle. This study, thus, provides new avenues to further investigate the specific role of N protein phosphorylation in CoV replication.
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