ArticleThe Journal of experimental medicine2001
Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 145 citations in OpenAlex.
- DRAM triggers lysosomal membrane permeabilization and cell death in CD4(+) T cells infected with HIV.PLoS pathogens · 2013Trial
- Review
- Human Immunodeficiency Virus Related Non-Hodgkin's Lymphoma.Blood and lymphatic cancer : targets and therapy · 2023Review
- The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence.Clinical microbiology reviews · 2019Review
- Rapamycin prevents cerebral stroke by modulating apoptosis and autophagy in penumbra in rats.Annals of clinical and translational neurology · 2018Article
- Arterial Infusion of Rapamycin in the Treatment of Rabbit Hepatocellular Carcinoma to Improve the Effect of TACE.Open life sciences · 2018Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
- The mTOR signal regulates myeloid-derived suppressor cells differentiation and immunosuppressive function in acute kidney injury.Cell death & disease · 2017Article
- Pivotal Role of Receptor-Interacting Protein Kinase 1 and Mixed Lineage Kinase Domain-Like in Neuronal Cell Death Induced by the Human Neuroinvasive Coronavirus OC43.Journal of virology · 2017Article
- Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model.PLoS pathogens · 2016Article
- A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy.The Journal of biological chemistry · 2015Article
- Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview.Cell death & disease · 2015Review
- Stress-mediated Sin3B activation leads to negative regulation of subset of p53 target genes.Bioscience reports · 2015Article
- DNA damage-induced S and G2/M cell cycle arrest requires mTORC2-dependent regulation of Chk1.Oncotarget · 2015Article
- Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives.Frontiers in immunology · 2015Review
- Rapamycin protects kidney against ischemia reperfusion injury through recruitment of NKT cells.Journal of translational medicine · 2014Article
- Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage.Journal of biomedical research · 2014Article
- Making sense of how HIV kills infected CD4 T cells: implications for HIV cure.Molecular and cellular therapies · 2014Review
- Anti-apoptotic mechanisms of HIV: lessons and novel approaches to curing HIV.Cellular and molecular life sciences : CMLS · 2013Review
- mTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN.American journal of physiology. Renal physiology · 2013Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Syncytia arising from the fusion of cells expressing a lymphotropic human immunodeficiency virus (HIV)-1-encoded envelope glycoprotein complex (Env) gene with cells expressing the CD4/CXCR4 complex undergo apoptosis through a mitochondrion-controlled pathway initiated by the upregulation of Bax. In syncytial apoptosis, phosphorylation of p53 on serine 15 (p53S15) precedes Bax upregulation, the apoptosis-linked conformational change of Bax, the insertion of Bax in mitochondrial membranes, subsequent release of cytochrome c, caspase activation, and apoptosis. p53S15 phosphorylation also occurs in vivo, in HIV-1(+) donors, where it can be detected in preapoptotic and apoptotic syncytia in lymph nodes, as well as in peripheral blood mononuclear cells, correlating with viral load. Syncytium-induced p53S15 phosphorylation is mediated by the upregulation/activation of mammalian target of rapamycin (mTOR), also called FKBP12-rapamycin-associated protein (FRAP), which coimmunoprecipitates with p53. Inhibition of mTOR/FRAP by rapamycin reduces apoptosis in several paradigms of syncytium-dependent death, including in primary CD4(+) lymphoblasts infected by HIV-1. Concomitantly, rapamycin inhibits p53S15 phosphorylation, mitochondrial translocation of Bax, loss of the mitochondrial transmembrane potential, mitochondrial release of cytochrome c, and nuclear chromatin condensation. Transfection with dominant negative p53 has a similar antiapoptotic action as rapamycin, upstream of the Bax upregulation/translocation. In summary, we demonstrate that phosphorylation of p53S15 by mTOR/FRAP plays a critical role in syncytial apoptosis driven by HIV-1 Env.
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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.