ArticlePloS one2008
Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 79 citations in OpenAlex.
- Review
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- Distinct Oncogenic Transcriptomes in Human Mammary Epithelial Cells Infected With Cytomegalovirus.Frontiers in immunology · 2021Article
- Reassessment of the capacity of the HIV-1 Env cytoplasmic domain to trigger NF-κB activation.Virology journal · 2018Article
- HIV-1 Tat potently stabilises Mdm2 and enhances viral replication.The Biochemical journal · 2017Article
- Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview.Cell death & disease · 2015Review
- The DNA damage response induced by infection with human cytomegalovirus and other viruses.Viruses · 2014Review
- A novel DDB2-ATM feedback loop regulates human cytomegalovirus replication.Journal of virology · 2014Article
- Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1)-infected CD4+ T lymphocytes.PloS one · 2014Article
- T-Cell Signaling in HIV-1 Infection.The open virology journal · 2013Article
- Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis.PloS one · 2013Article
- P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance.Oncogene · 2012Article
- Targeting HIV-1 gp41-induced fusion and pathogenesis for anti-viral therapy.Current topics in medicinal chemistry · 2011Review
- Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection.The Journal of experimental medicine · 2011Article
- CD4+ T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis.Viruses · 2011Review
- Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice.Virology journal · 2011Article
- Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response.Immunologic research · 2010Review
- HIV infection upregulates caveolin 1 expression to restrict virus production.Journal of virology · 2010Article
- Redox mechanisms involved in the selective activation of Nrf2-mediated resistance versus p53-dependent apoptosis in adenocarcinoma cells.The Journal of biological chemistry · 2009Article
- Exploiting synthetic lethal interactions for targeted cancer therapy.Cell cycle (Georgetown, Tex.) · 2009Review
Corrections and comments
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Authors and funding
21 authors at 12 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM), which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes an activating phosphorylation in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. This was accompanied by aggregation of ATM in discrete nuclear foci that also contained phospho-histone H2AX. DNA damage foci containing phosphorylated ATM and H2AX were detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Knockdown of ATM or of its obligate activating factor NBS1 (Nijmegen breakage syndrome 1 protein), as well as pharmacological inhibition of ATM with KU-55933, inhibited H2AX phosphorylation and prevented Env-elicited syncytia from undergoing apoptosis. ATM was found indispensable for the activation of MAP kinase p38, which catalyzes the activating phosphorylation of p53 on serine 46, thereby causing p53 dependent apoptosis. Both wild type HIV-1 and an HIV-1 mutant lacking integrase activity induced syncytial apoptosis, which could be suppressed by inhibiting ATM. HIV-1-infected T lymphoblasts from patients with inactivating ATM or NBS1 mutations also exhibited reduced syncytial apoptosis. Altogether these results indicate that apoptosis induced by a fusogenic HIV-1 Env follows a pro-apoptotic pathway involving the sequential activation of ATM, p38MAPK and p53.
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