ArticleProceedings of the National Academy of Sciences of the United States of America2014
STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell proliferation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- Poly (ADP-Ribose) Polymerase 1 and 2 in B-Cell Lymphoma: Pathogenic Roles and Therapeutic Implications.The American journal of pathology · 2025Review
- Claspin and Cancer: Where Are We Now?International journal of molecular sciences · 2025Review
- Insights into absence of lymphoma despite fulminant Epstein-Barr virus infection in patients with XIAP deficiency.JCI insight · 2025Article
- STAT3, MYC, and EBNA1 cooperate through a ZC3H18 transcriptional network to regulate survival and proliferation of EBV-positive lymphomas.PLoS pathogens · 2025Article
- Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibition in breast cancer.Nature communications · 2025Article
- Intrinsic p53 activation restricts gammaherpesvirus driven germinal center B cell expansion during latency establishment.Nature communications · 2025Article
- Polymerase theta is a synthetic lethal target for killing Epstein-Barr virus lymphomas.Journal of virology · 2024Article
- Non-canonical role for the ataxia-telangiectasia-Rad3 pathway in STAT3 activation in human multiple myeloma cells.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Loss of IRF8 inhibits the growth of acute myeloid leukemia cells.Annals of hematology · 2023Article
- Galectin-9 Facilitates Epstein-Barr Virus Latent Infection and Lymphomagenesis in Human B Cells.Microbiology spectrum · 2023Article
- FIBP interacts with transcription factor STAT3 to induce EME1 expression and drive radioresistance in lung adenocarcinoma.International journal of biological sciences · 2023Article
- Receptor interacting protein 1 knockdown induces cell death in liver cancer by suppressing STAT3/ATR activation in a p53-dependent manner.American journal of cancer research · 2022Article
- Article
- Review
- Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91.Journal of medicinal chemistry · 2021Article
- Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis.Frontiers in allergy · 2021Article
- Periodontal Pathogens Promote Oral Squamous Cell Carcinoma by Regulating ATR and NLRP3 Inflammasome.Frontiers in oncology · 2021Article
- An Ancestral Retrovirus Envelope Protein Regulates Persistent Gammaherpesvirus Lifecycles.Frontiers in microbiology · 2021Article
- Cardiac Glycoside Ouabain Exerts Anticancer ActivityFrontiers in oncology · 2021Article
- STAT3 imparts BRCAness by impairing homologous recombination repair in Epstein-Barr virus-transformed B lymphocytes.PLoS pathogens · 2020Article
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Authors and funding
9 authors at 8 institutions in 2 countries.
Funding
Abstract
DNA damage response (DDR) is a signaling network that senses DNA damage and activates response pathways to coordinate cell-cycle progression and DNA repair. Thus, DDR is critical for maintenance of genome stability, and presents a powerful defense against tumorigenesis. Therefore, to drive cell-proliferation and transformation, viral and cellular oncogenes need to circumvent DDR-induced cell-cycle checkpoints. Unlike in hereditary cancers, mechanisms that attenuate DDR and disrupt cell-cycle checkpoints in sporadic cancers are not well understood. Using Epstein-Barr virus (EBV) as a source of oncogenes, we have previously shown that EBV-driven cell proliferation requires the cellular transcription factor STAT3. EBV infection is rapidly followed by activation and increased expression of STAT3, which mediates relaxation of the intra-S phase cell-cycle checkpoint; this facilitates viral oncogene-driven cell proliferation. We now show that replication stress-associated DNA damage, which results from EBV infection, is detected by DDR. However, signaling downstream of ATR is impaired by STAT3, leading to relaxation of the intra-S phase checkpoint. We find that STAT3 interrupts ATR-to-Chk1 signaling by promoting loss of Claspin, a protein that assists ATR to phosphorylate Chk1. This loss of Claspin which ultimately facilitates cell proliferation is mediated by caspase 7, a protein that typically promotes cell death. Our findings demonstrate how STAT3, which is constitutively active in many human cancers, suppresses DDR, fundamental to tumorigenesis. This newly recognized role for STAT3 in attenuation of DDR, discovered in the context of EBV infection, is of broad interest as the biology of cell proliferation is central to both health and disease.
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