ArticleCell death and differentiation2020
HPV-mediated nuclear export of HP1γ drives cervical tumorigenesis by downregulation of p53.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Identification and validation of a thirteen-gene signature based on ubiquitin related genes in cervical cancer.Discover oncology · 2025Article
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Precision therapeutic targets for HPV-positive cancers: an overview and new insights.Infectious agents and cancer · 2025Review
- Induction of the p21/CDK6 pathway and alteration of the immune microenvironment by the stem cell marker CBX3 in melanoma.Stem cell research & therapy · 2025Article
- Systematic Analysis of E3 Ligase-Related Genes Identified UBE2L3 as a Prognostic Biomarker Associated With Drug Resistance in Acute Myeloid Leukemia.International journal of general medicine · 2025Article
- UBE2L3 expression in human gastric cancer and its clinical significance.Journal of cancer research and clinical oncology · 2024Article
- Exploring the causal association between rheumatoid arthritis and the risk of cervical cancer: a two-sample Mendelian randomization study.Arthritis research & therapy · 2024Article
- Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions.MedComm · 2023Review
- A functional crosstalk between the H3K9 methylation writers and their reader HP1 in safeguarding embryonic stem cell identity.Stem cell reports · 2023Article
- HPV18 E6 inhibits α-ketoglutarate-induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway.FEBS open bio · 2023Article
- Transcriptomic analysis of the effects of the HPV18 E6E7 gene on the cell death mode in esophageal squamous cell carcinoma.Oncology letters · 2023Article
- Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review).International journal of oncology · 2023Review
- Article
- High-throughput functional evaluation of human cancer-associated mutations using base editors.Nature biotechnology · 2022Article
- Review
- Mechanism and Disease Association With a Ubiquitin Conjugating E2 Enzyme: UBE2L3.Frontiers in immunology · 2022Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- Transcriptomics-Based Repositioning of Natural Compound, Eudesmin, as a PRC2 Modulator.Molecules (Basel, Switzerland) · 2021Article
- Metabolic Control by DNA Tumor Virus-Encoded Proteins.Pathogens (Basel, Switzerland) · 2021Review
- Morolic Acid 3-Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
E6 oncoprotein derived from high-risk human papillomavirus (HPV) drives the development of cervical cancer through p53 degradation. Because cervical cancer therapies to inactivate HPV or E6 protein are not available, alternative strategies are required. Here, we show that HPV-mediated nuclear export of human heterochromatin protein 1γ (HP1γ) reduces the stability of p53 through UBE2L3-mediated p53 polyubiquitination during cervical cancer progression. In general, HP1 plays a key role in heterochromatin formation and transcription in the nucleus. However, our immunostaining data showed that the majority of HP1γ is localized in the cytoplasm in HPV-mediated cervical cancer. We found that HPV E6 protein drives unusual nuclear export of HP1γ through the interaction between the NES sequence of HP1γ and exportin-1. The mutation of the NES sequence in HP1γ led to nuclear retention of HP1γ and reduced cervical cancer cell growth and tumor generation. We further discovered that HP1γ directly suppresses the expression of UBE2L3 which drives E6-mediated proteasomal degradation of p53 in cervical cancer. Downregulation of UBE2L3 by overexpression of HP1γ suppressed UBE2L3-dependent p53 degradation-promoting apoptosis of cervical cancer cells. Our findings propose a useful strategy to overcome p53 degradation in cervical cancer through the blockage of nuclear export of HP1γ.
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