ArticleMolecular and cellular biology2013
DNA damage regulates UHRF1 stability via the SCF(β-TrCP) E3 ligase.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Novel function of GTPBP2 in promoting hepatocellular carcinoma progression through inhibition of BTRC-mediated KRAS degradation.Cancer cell international · 2026Article
- Advances in post-translational and epigenetic modification of hyperuricemia-to-gout progression: mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Development of a novel 4-protein signature for prognostic prediction in hepatitis B virus-induced hepatocellular carcinoma.Discover oncology · 2025Article
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- SIRT6 deficiency impairs the deacetylation and ubiquitination of UHRF1 to strengthen glycolysis and lactate secretion in bladder cancer.Cell & bioscience · 2024Article
- STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A.Journal of experimental & clinical cancer research : CR · 2024Article
- The emerging and diverse roles of F-box proteins in spermatogenesis and male infertility.Cell regeneration (London, England) · 2024Review
- Roles of post-translational modifications of UHRF1 in cancer.Epigenetics & chromatin · 2024Review
- Enhanced Transcriptional Signature and Expression of Histone-Modifying Enzymes in Salivary Gland Tumors.Cells · 2023Article
- Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1.Molecules (Basel, Switzerland) · 2023Review
- An shRNA kinase screen identifies regulators of UHRF1 stability and activity in mouse embryonic stem cells.Epigenetics · 2022Article
- UHRF1 interacts with snRNAs and regulates alternative splicing in mouse spermatogonial stem cells.Stem cell reports · 2022Article
- TIP60 governs the auto‑ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex.International journal of oncology · 2021Article
- The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity.Nucleic acids research · 2021Review
- Staying true to yourself: mechanisms of DNA methylation maintenance in mammals.Nucleic acids research · 2021Review
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- Methylation of UHRF1 by SET7 is essential for DNA double-strand break repair.Nucleic acids research · 2019Article
- Epigenetic mechanism and target therapy of UHRF1 protein complex in malignancies.OncoTargets and therapy · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
UHRF1 (ubiquitin-like, with PHD and RING finger domains 1) is a critical epigenetic player involved in the maintenance of DNA methylation patterns during DNA replication. Dysregulation of the UHRF1 level is implicated in cancer onset, metastasis, and tumor recurrence. Previous studies demonstrated that UHRF1 can be stabilized through USP7-mediated deubiquitylation, but the mechanism through which UHRF1 is ubiquitylated is still unknown. Here we show that proteasomal degradation of UHRF1 is mediated by the SCF(β-TrCP) E3 ligase. Through bioinformatic and mutagenesis studies, we identified a functional DSG degron in the UHRF1 N terminus that is necessary for UHRF1 stability regulation. We further show that UHRF1 physically interacts with β-TrCP1 in a manner dependent on phosphorylation of serine 108 (S108(UHRF1)) within the DSG degron. Furthermore, we demonstrate that S108(UHRF1) phosphorylation is catalyzed by casein kinase 1 delta (CK1δ) and is important for the recognition of UHRF1 by SCF(β-TrCP). Importantly, we demonstrate that UHRF1 degradation is accelerated in response to DNA damage, coincident with enhanced S108(UHRF1) phosphorylation. Taken together, our data identify SCF(β-TrCP) as a bona fide UHRF1 E3 ligase important for regulating UHRF1 steady-state levels both under normal conditions and in response to DNA damage.
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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.