ArticleProceedings of the National Academy of Sciences of the United States of America2010
Alternative splicing of human papillomavirus type-16 E6/E6* early mRNA is coupled to EGF signaling via Erk1/2 activation.
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 62 papers.
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Who cites it
62 citing papers in PubMed, 90 citations in OpenAlex.
- Review
- Establishment of an immortalized erythroid model for Hb Bart's hydrops fetalis with homozygous αScientific reports · 2026Article
- Human papillomavirus 16 E6 oncoprotein promotes up-regulation of RNA-binding protein Sam68 in head and neck cancer.Frontiers in microbiology · 2026Article
- Review
- Viruses exploit growth factor mechanisms to achieve augmented pathogenicity and promote tumorigenesis.Archives of microbiology · 2024Review
- Alternative splicing in the genome of HPV and its regulation.Frontiers in cellular and infection microbiology · 2024Review
- hnRNP K induces HPV16 oncogene expression and promotes cervical cancerization.Journal of cancer research and clinical oncology · 2023Article
- Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?International journal of molecular sciences · 2022Review
- Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets.Cell death discovery · 2022Review
- The splicing factor SF3B4 drives proliferation and invasion in cervical cancer by regulating SPAG5.Cell death discovery · 2022Article
- It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer.Cancers · 2022Review
- HPV16 and HPV18 Genome Structure, Expression, and Post-Transcriptional Regulation.International journal of molecular sciences · 2022Review
- hnRNP G/RBMX enhances HPV16 E2 mRNA splicing through a novel splicing enhancer and inhibits production of spliced E7 oncogene mRNAs.Nucleic acids research · 2022Article
- Overexpression of m6A-factors METTL3, ALKBH5, and YTHDC1 alters HPV16 mRNA splicing.Virus genes · 2022Article
- Identification of heterogenous nuclear ribonucleoproteins (hnRNPs) and serine- and arginine-rich (SR) proteins that induce human papillomavirus type 16 late gene expression and alter L1 mRNA splicing.Archives of virology · 2022Article
- High-Risk Human Papillomavirus Oncogenic E6/E7 mRNAs Splicing Regulation.Frontiers in cellular and infection microbiology · 2022Review
- Construction of an immune-related ceRNA network in cervical cancer based on HPV E6 splicing.Frontiers in oncology · 2022Article
- Differential Incidence of Tongue Base Cancer in Male and Female HPV16-Transgenic Mice: Role of Female Sex Hormone Receptors.Pathogens (Basel, Switzerland) · 2021Article
- Observational
- MEK/ERK signaling is a critical regulator of high-risk human papillomavirus oncogene expression revealing therapeutic targets for HPV-induced tumors.PLoS pathogens · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Certain types of human papillomaviruses (HPVs) are etiologically linked to cervical cancer. Their transforming capacity is encoded by a polycistronic premRNA, where alternative splicing leads to the translation of functional distinct proteins such as E6, E6*, and E7. Here we show that splicing of HPV16 E6/E7 ORF cassette is regulated by the epidermal growth factor (EGF) pathway. The presence of EGF was coupled to preferential E6 expression, whereas depletion of EGF, or treatment with EGF receptor (EGFR) neutralizing antibodies or the EGFR inhibitor tyrphostin AG1478, resulted in E6 exon exclusion in favor of E6*. As a consequence, increased p53 levels and enhanced translation of E7 with a subsequent reduction of the retinoblastoma protein pRb could be discerned. E6 exon exclusion upon EGF depletion was independent from promoter usage, mRNA stability, or selective mRNA transport. Time-course experiments and incubation with cycloheximide demonstrated that E6 alternative splicing is a direct and reversible effect of EGF signal transduction, not depending on de novo protein synthesis. Within this process, Erk1/2-kinase activation was the critical event for E6 exon inclusion, mediated by the upstream MAP kinase MEK1/2. Moreover, siRNA knockdown experiments revealed an involvement of splicing factors hnRNPA1 and hnRNPA2 in E6 exon exclusion, whereas the splicing factors Brm and Sam68 were found to promote E6 exon inclusion. Because there is a natural gradient of EGF and EGF receptor expression in the stratified epithelium, it is reasonable to assume that EGF modulates E6/E7 splicing during the viral life cycle and transformation.
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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.