ArticleScientific reports2017
Avian reovirus p17 and σA act cooperatively to downregulate Akt by suppressing mTORC2 and CDK2/cyclin A2 and upregulating proteasome PSMB6.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- GNL2 plays a critical role in avian reovirus p17-mediated host cellular autophagy and promotes viral proliferation.Poultry science · 2026Article
- Proteome Microarray-Guided Global View: Multiple Pharmacological Targets of Icariin.Drug design, development and therapy · 2026Article
- The oncolytic avian reovirus p17 protein triggers chaperone-mediated autophagy by modulating Hsp90 and the T-complex protein-1 ring complex chaperones and co-chaperones to activate the IKK/NF-κB signaling.Journal of virology · 2025Article
- Annexin A2 stabilizes the endoplasmic reticulum and actin cytoskeleton and influences the formation of reovirus factories.Journal of virology · 2025Article
- Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?Molecular neurobiology · 2025Review
- The mechanism of action of micafungin against pteropine orthoreovirus infection in the human A549 cell line.Archives of virology · 2025Article
- Review
- Article
- Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response.Frontiers in cellular and infection microbiology · 2023Review
- Oncolytic Avian Reovirus p17-Modulated Inhibition of mTORC1 by Enhancement of Endogenous mTORC1 Inhibitors Binding to mTORC1 To Disrupt Its Assembly and Accumulation on Lysosomes.Journal of virology · 2022Article
- Gga-miR-30c-5p Suppresses Avian Reovirus (ARV) Replication by Inhibition of ARV-Induced Autophagy via Targeting ATG5.Journal of virology · 2022Article
- Identification and Functional Analyses of Host Proteins Interacting with the p17 Protein of Avian Reovirus.Viruses · 2022Article
- p17-Modulated Hsp90/Cdc37 Complex Governs Oncolytic Avian Reovirus Replication by Chaperoning p17, Which Promotes Viral Protein Synthesis and Accumulation of Viral Proteins σC and σA in Viral Factories.Journal of virology · 2022Article
- The Multi-Faceted Role of Autophagy During Animal Virus Infection.Frontiers in cellular and infection microbiology · 2022Review
- Viral Proteins as Emerging Cancer Therapeutics.Cancers · 2021Review
- Article
- Construction of polycistronic baculovirus surface display vectors to express the PCV2 Cap(d41) protein and analysis of its immunogenicity in mice and swine.Veterinary research · 2020Article
- Aspirin and 5-Aminoimidazole-4-carboxamide Riboside Attenuate Bovine Ephemeral Fever Virus Replication by Inhibiting BEFV-Induced Autophagy.Frontiers in immunology · 2020Article
- Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers.Infectious agents and cancer · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although we have shown that avian reovirus (ARV) p17-mediated inhibition of Akt leads to induction of autophagy, the precise mechanisms remain largely unknown. This study has identified a specific mechanism by which ARV coordinately regulates the degradation of ribosomal proteins by p17-mediated activation of E3 ligase MDM2 that targets ribosomal proteins and by σA-mediated upregulation of proteasome PSMB6. In addition to downregulating ribosomal proteins, p17 reduces mTORC2 assembly and disrupts mTORC2-robosome association, both of which inactivate mTORC2 leading to inhibition of Akt phosphorylation at S473. Furthermore, we discovered that p17 binds to and inhibits the CDK2/cyclin A2 complex, further inhibiting phosphorylation of Akt S473. The negative effect of p17 on mTORC2 assembly and Akt phosphorylation at S473 is reversed in cells treated with insulin or overexpression of CDK2. The carboxyl terminus of p17 is necessary for interaction with CDK2 and for induction of autophagy. Furthermore, p17-mediated upregulation of LC3-II could be partially reversed by overexpression of CDK2. The present study provides mechanistic insights into cooperation between p17 and σA proteins of ARV to negatively regulate Akt by downregulating complexes of mTORC2 and CDK2/cyclin A2 and upregulating PSMB6, which together induces autophagy and cell cycle arrest and benefits virus replication.
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