ArticleProceedings of the National Academy of Sciences of the United States of America2010
Adenovirus 12 E4orf6 inhibits ATR activation by promoting TOPBP1 degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. 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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60 citing papers in PubMed, 74 citations in OpenAlex.
- The FACT complex associates with the RPA complex at viral replication compartments to promote adenovirus infection.Journal of virology · 2026Article
- Seneca Valley virus infection exploits DNA damage response to facilitate viral replication.Journal of virology · 2025Article
- Pathogenicity and virulence of human adenovirus F41: Possible links to severe hepatitis in children.Virulence · 2023Review
- Identification of Adenovirus E1B-55K Interaction Partners through a Common Binding Motif.Viruses · 2023Article
- The consequences of viral infection on host DNA damage response: a focus on SARS-CoVs.Journal, genetic engineering & biotechnology · 2022Review
- Mouse Adenovirus Type 1 E4orf6 Induces PKR Degradation.Journal of virology · 2022Article
- Article
- Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases.Experimental & molecular medicine · 2020Review
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- The Role of Ataxia Telangiectasia Mutant and Rad3-Related DNA Damage Response in Pathogenesis of Human Papillomavirus.Pathogens (Basel, Switzerland) · 2020Review
- The 6-4 photoproduct is the trigger of UV-induced replication blockage and ATR activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Adenoviral strategies to overcome innate cellular responses to infection.FEBS letters · 2019Review
- Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Article
- Adenovirus E1B 55-Kilodalton Protein Targets SMARCAL1 for Degradation during Infection and Modulates Cellular DNA Replication.Journal of virology · 2019Article
- Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3.Journal of virology · 2019Article
- Ubiquitination at the interface of tumor viruses and DNA damage responses.Current opinion in virology · 2018Review
- Virus DNA Replication and the Host DNA Damage Response.Annual review of virology · 2018Review
- Degradation of a Novel DNA Damage Response Protein, Tankyrase 1 Binding Protein 1, following Adenovirus Infection.Journal of virology · 2018Article
- Serotype-specific restriction of wild-type adenoviruses by the cellular Mre11-Rad50-Nbs1 complex.Virology · 2018Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the cellular DNA damage response is detrimental to adenovirus (Ad) infection. Ad has therefore evolved a number of strategies to inhibit ATM- and ATR-dependent signaling pathways during infection. Recent work suggests that the Ad5 E4orf3 protein prevents ATR activation through its ability to mislocalize the MRN complex. Here we provide evidence to indicate that Ad12 has evolved a different strategy from Ad5 to inhibit ATR. We show that Ad12 utilizes a CUL2/RBX1/elongin C-containing ubiquitin ligase to promote the proteasomal degradation of the ATR activator protein topoisomerase-IIbeta-binding protein 1 (TOPBP1). Ad12 also uses this complex to degrade p53 during infection, in contrast to Ad5, which requires a CUL5-based ubiquitin ligase. Although Ad12-mediated degradation of p53 is dependent upon both E1B-55K and E4orf6, Ad12-mediated degradation of TOPBP1 is solely dependent on E4orf6. We propose that Ad12 E4orf6 has two principal activities: to recruit the CUL2-based ubiquitin ligase and to act as substrate receptor for TOPBP1. In support of the idea that Ad12 E4orf6 specifically prevents ATR activation during infection by targeting TOPBP1 for degradation, we demonstrate that Ad12 E4orf6 can inhibit the ATR-dependent phosphorylation of CHK1 in response to replication stress. Taken together, these data provide insights into how Ad modulates ATR signaling pathways during infection.
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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.