ArticleProceedings of the National Academy of Sciences of the United States of America2006
Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 110 citations in OpenAlex.
- Article
- Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice.PLoS pathogens · 2024Article
- Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.Science signaling · 2024Article
- MicroRNAs in infectious diseases: potential diagnostic biomarkers and therapeutic targets.Clinical microbiology reviews · 2023Review
- In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023Article
- Article
- The Akt Forkhead Box O Transcription Factor Axis Regulates Human Cytomegalovirus Replication.mBio · 2022Article
- Postnatal Cytomegalovirus Infection May Increase the Susceptibility of Tuberous Sclerosis Complex to Autism Spectrum Disorders.Microbiology spectrum · 2022Article
- Downregulation of neurodevelopmental gene expression in iPSC-derived cerebral organoids upon infection by human cytomegalovirus.iScience · 2022Article
- Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication.Frontiers in cellular and infection microbiology · 2022Article
- An RNA-RNA crosstalk network involving HMGB1 and RICTOR facilitates hepatocellular carcinoma tumorigenesis by promoting glutamine metabolism and impedes immunotherapy by PD-L1+ exosomes activity.Signal transduction and targeted therapy · 2021Article
- Article
- Mechanistic Target of Rapamycin Signaling Activation Antagonizes Autophagy To Facilitate Zika Virus Replication.Journal of virology · 2020Article
- Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy.Current hematologic malignancy reports · 2020Review
- Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease.PLoS genetics · 2020Article
- Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.Viruses · 2020Review
- Resistance of THP-1 Leukemia Cells Infected with Cytomegalovirus to Anti-tumor Antibiotic Doxorubicin and Restoration of the Sensitivity by Inhibitors of the PI3K/AKT/mTOR Molecular Pathway.Doklady. Biochemistry and biophysics · 2019Article
- Common Mechanisms of Viral Injury to the Kidney.Advances in chronic kidney disease · 2019Review
- Review
- Chewing the Fat: The Conserved Ability of DNA Viruses to Hijack Cellular Lipid Metabolism.Viruses · 2019Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Signaling mediated by the mammalian target of rapamycin kinase (mTOR) is activated during human cytomegalovirus (HCMV) infection. mTOR is found in two complexes differing by the binding partner, rictor or raptor. Activated mTOR-raptor promotes cap-dependent translation through the hyperphosphorylation of the eIF4E-binding protein (4E-BP). This activity of the raptor complex is normally inhibited by cell stress responses or the drug rapamycin. However, we previously showed that this inhibition of mTOR signaling can be circumvented during HCMV infection such that hyperphosphorylation of 4E-BP is maintained. Here we show that HCMV infection also activates the rictor complex, as indicated by increased phosphorylation of Akt S473; this phosphorylation is insensitive to rapamycin but sensitive to caffeine in both uninfected and infected cells. By using short-hairpin RNAs to deplete rictor and raptor, we find that rictor is more significant than raptor for the viral infection. Surprisingly, the inhibitory effects of rapamycin on viral growth are primarily due to the presence of rictor, not raptor. Raptor and rictor depletion experiments show that in HCMV-infected cells, both raptor- and rictor-containing complexes can mediate the hyperphosphorylation of 4E-BP and the phosphorylation of p70S6 kinase. Under these conditions, the rictor complex is rapamycin-sensitive for the hyperphosphorylation of 4E-BP, but the raptor complex is not. These data suggest that, during HCMV infection, the rictor- and raptor-containing complexes are modified such that their substrate specificities and rapamycin sensitivities are altered. Our data also suggest that the present understanding of rapamycin's inhibitory effects is incomplete.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.