ArticleOncogene2013
The epigenetic regulator UHRF1 promotes ubiquitination-mediated degradation of the tumor-suppressor protein promyelocytic leukemia protein.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells.Cell death & disease · 2018Pooled it
- UHRF1 as an epigenetic therapeutic target in Cancer.Molecular biology reports · 2026Review
- UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.Nature communications · 2025Article
- UHRF1 in endothelial cells is essential for angiogenesis and associated with the activation of pro-angiogenic signaling pathways and expression of endothelial genes.Angiogenesis · 2025Article
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
- RAD51 plays critical roles in DNMT1-mediated maintenance methylation of genomic DNA by dually regulating the ubiquitin ligase UHRF1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Roles of post-translational modifications of UHRF1 in cancer.Epigenetics & chromatin · 2024Review
- On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the Biogenesis of PML-Bodies.Biomolecules · 2023Article
- Downregulation of DNA methylation enhances differentiation of THP-1 cells and induces M1 polarization of differentiated macrophages.Scientific reports · 2023Article
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- An shRNA kinase screen identifies regulators of UHRF1 stability and activity in mouse embryonic stem cells.Epigenetics · 2022Article
- UHRF1 overexpression promotes osteosarcoma metastasis through altered exosome production and AMPK/SEMA3E suppression.Oncogenesis · 2022Article
- Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia.Cancers · 2022Article
- EZH2 restrictsFrontiers in immunology · 2022Article
- TIP60 governs the auto‑ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex.International journal of oncology · 2021Article
- The hepatocyte clock and feeding control chronophysiology of multiple liver cell types.Science (New York, N.Y.) · 2020Article
- Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1.BMC biology · 2020Article
- The Rare Variant rs35356162 inFrontiers in oncology · 2020Article
- ADAMTS8 Inhibits Cell Proliferation and Invasion, and Induces Apoptosis in Breast Cancer.OncoTargets and therapy · 2020Article
- Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.Molecular & cellular proteomics : MCP · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The promyelocytic leukemia (PML) protein is a tumor suppressor originally identified in acute promyelocytic leukemia and implicated in tumorigenesis in multiple forms of cancer. Here, we demonstrate that the PML protein undergoes ubiquitination-mediated degradation facilitated by an E3 ligase UHRF1 (ubiquitin-like with PHD and RING finger domains 1), which is commonly upregulated in various human malignancies. Furthermore, UHRF1 negatively regulates PML protein accumulation in primary human umbilical vein endothelial cells (HUVECs), HEK 293 cells and cancer cells. Knockdown of UHRF1 upregulates whereas ectopic overexpression of UHRF1 downregulates protein abundance of endogenous or exogenous PML, doing so through its binding to the N-terminus of PML. Overexpression of wild-type UHRF1 shortens PML protein half-life and promotes PML polyubiquitination, whereas deletion of the RING domain or coexpression of the dominant-negative E2 ubiquitin-conjugating enzyme, E2D2, attenuates this modification to PML. Finally, knockdown of UHRF1 prolongs PML half-life and increases PML protein accumulation, yet inhibits cell migration and in vitro capillary tube formation, whereas co-knockdown of PML compromises this inhibitory effect. These findings suggest that UHRF1 promotes the turnover of PML protein, and thus targeting UHRF1 to restore PML-mediated tumor suppression represents a promising, novel, anticancer strategy.
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