ArticleScientific reports2019
Activated MEK/ERK Pathway Drives Widespread and Coordinated Overexpression of UHRF1 and DNMT1 in Cancer cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- UHRF1 inhibits cuproptosis in lung adenocarcinoma via promoting FDX1 promoter methylation.Respiratory research · 2026Article
- Prenatal and Lactational Exposure to Polystyrene Nanoplastics Induces Lipid Accumulation in Vascular Smooth Muscle Cells of Male Offspring via the MAPK/ERK/UHRF1 Signaling Pathway.Cardiovascular toxicology · 2026Article
- Unravelling chemotherapeutic activity of fisetin ruthenium-p-cymene complex in lung cancer treatment by the modulation of GRB2/RAS/MEK/DNMT1 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A Further Case for Targeting PRMT5 and the ERK1/2 and PI3K Pathways in CRC.International journal of molecular sciences · 2025Article
- E2F1 suppresses Epstein-Barr virus lytic reactivation through cellular and viral transcriptional networks.PLoS pathogens · 2025Article
- IL-17A Induces Circadian Disruptions Through the Epigenetic Repression of BMAL1 in Mice With Alzheimer's Disease.Journal of cellular and molecular medicine · 2025Article
- DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy.Molecular biology reports · 2024Article
- Roles of post-translational modifications of UHRF1 in cancer.Epigenetics & chromatin · 2024Review
- CRISPR-Cas9 screening develops an epigenetic and transcriptional gene signature for risk stratification and target prediction in neuroblastoma.Frontiers in cell and developmental biology · 2024Article
- The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia.Pathology oncology research : POR · 2024Article
- Exploring acenocoumarol and silodosin in non-small cell lung cancer: Insights into EGFR-linked signaling mechanisms.F1000Research · 2024Article
- Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1.Molecules (Basel, Switzerland) · 2023Review
- SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.Cell reports · 2023Article
- UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma.Nature communications · 2023Article
- NUP98 and RAE1 sustain progenitor function through HDAC-dependent chromatin targeting to escape from nucleolar localization.Communications biology · 2023Article
- Regulatory mechanism and biological function of UHRF1-DNMT1-mediated DNA methylation.Functional & integrative genomics · 2022Review
- An shRNA kinase screen identifies regulators of UHRF1 stability and activity in mouse embryonic stem cells.Epigenetics · 2022Article
- DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation.Annals of medicine · 2022Review
- ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression.Cell death and differentiation · 2022Article
- E2F1-mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10.Cancer science · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The UHRF1-DNMT1 axis plays a key role in DNA maintenance methylation in mammals. Accumulative studies demonstrate that UHRF1 is broadly overexpressed in cancers, which contributes to cancer cell proliferation and tumorigenesis. Interestingly, a proteasome-dependent downregulation of UHRF1 has been observed in pluripotent ground state mouse embryonic stem cells (mESCs) cultured in the presence of two kinase (MEK1/MEK2 and GSK3β) inhibitors (termed 2i), raising the question whether UHRF1 is similarly regulated in cancer cells. Here we present evidence that while addition of 2i broadly downregulates UHRF1 and DNMT1 in various cancer cells, distinct underlying mechanisms are involved. In contrast to mESCs, 2i-induced downregulation of UHRF1 and DNMT1 in cancer cells cannot be rescued by proteasome inhibitor and occurs primarily at the level of transcription. Furthermore, downregulation of UHRF1 and DNMT1 by 2i is due to inhibition of MEK1/MEK2, but not GSK3β activity. Data mining reveals a marked co-expression of UHRF1 and DNMT1 in normal tissues as well as cancers. We provide evidence that multiple transcription factors including E2F1 and SP1 mediate the transcriptional activation of UHRF1 and DNMT1 by the activated MEK/ERK pathway. Together our study reveals distinct regulation of UHRF1/DNMT1 in mESCs and cancer cells and identifies activated MEK/ERK pathway as a driving force for coordinated and aberrant over-expression of UHRF1 and DNMT1 in cancers.
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