ArticleAging2009
The mRNA decay factor tristetraprolin (TTP) induces senescence in human papillomavirus-transformed cervical cancer cells by targeting E6-AP ubiquitin ligase.
Article in Aging, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Replicon-based genome-wide CRISPR knockout screening for the identification of host factors involved in viral replication.Nature communications · 2025Article
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- Foot-and-mouth disease virus (FMDV) negatively regulates ZFP36 protein expression to alleviate its antiviral activity.Journal of virology · 2024Article
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines.BMC cancer · 2024Article
- LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer through MBNL1-AS1/ZFP36/CENPA Axis.Journal of oncology · 2022Article
- Mechanisms and Regulation of Cellular Senescence.International journal of molecular sciences · 2021Review
- Identification of a novel iron zinc finger protein 36 (ZFP36) for predicting the overall survival of osteosarcoma based on the Gene Expression Omnibus (GEO) database.Annals of translational medicine · 2021Article
- Review
- The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects.Cancers · 2020Review
- The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1.Aging · 2019Article
- Tristetraprolin Is a Prognostic Biomarker for Poor Outcomes among Patients with Low-Grade Prostate Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Article
- Roles of Tristetraprolin in Tumorigenesis.International journal of molecular sciences · 2018Review
- LncRNA-OIS1 regulates DPP4 activation to modulate senescence induced by RAS.Nucleic acids research · 2018Article
- Shining the Light on Senescence Associated LncRNAs.Aging and disease · 2017Review
- Article
- Long Noncoding RNAs and RNA-Binding Proteins in Oxidative Stress, Cellular Senescence, and Age-Related Diseases.Oxidative medicine and cellular longevity · 2017Review
- Tristetraprolin disables prostate cancer maintenance by impairing proliferation and metabolic function.Oncotarget · 2016Article
- Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis.Oncotarget · 2016Article
- RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC.PLoS genetics · 2016Article
- A novel p70 S6 kinase-microRNA biogenesis axis mediates multicellular spheroid formation in ovarian cancer progression.Oncotarget · 2016Article
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3 authors at 2 institutions in 1 country.
Funding
Abstract
The RNA-binding protein tristetraprolin (TTP) regulates expression of many cancer-associated and proinflammatory factors through binding AU-rich elements (ARE) in the 3'-untranslated region (3'UTR) and facilitating rapid mRNA decay. Here we report on the ability of TTP to act in an anti-proliferative capacity in HPV18-positive HeLa cells by inducing senescence. HeLa cells maintain a dormant p53 pathway and elevated telomerase activity resulting from HPV-mediated transformation, whereas TTP expression counteracted this effect by stabilizing p53 protein and inhibiting hTERT expression. Presence of TTP did not alter E6 and E7 viral mRNA levels indicating that these are not TTP targets. It was found that TTP promoted rapid mRNA decay of the cellular ubiquitin ligase E6-associated protein (E6-AP). RNA-binding studies demonstrated TTP and E6-AP mRNA interaction and deletion of the E6-AP mRNA ARE-containing 3'UTR imparts resistance to TTP-mediated downregulation. Similar results were obtained with high-risk HPV16-positive cells that employ the E6-AP pathway to control p53 and hTERT levels. Furthermore, loss of TTP expression was consistently observed in cervical cancer tissue compared to normal tissue. These findings demonstrate the ability of TTP to act as a tumor suppressor by inhibiting the E6-AP pathway and indicate TTP loss to be a critical event during HPV-mediated carcinogenesis.
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Registered trials
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.