ArticleMolecular and cellular biology2013
ATM mediates pRB function to control DNMT1 protein stability and DNA methylation.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 0 citations in OpenAlex.
- UHRF1 overexpression generates distinct senescent states with different Tp53 dependencies.EMBO reports · 2026Article
- Breast tumors from ATM pathogenic variant carriers display a specific genome-wide DNA methylation profile.Breast cancer research : BCR · 2025Article
- Analysis of pathogenic variants in retinoblastoma reveals a potential gain of function mutation.Genes & cancer · 2025Article
- Article
- Interactions of circRNAs with methylation: An important aspect of circRNA biogenesis and function (Review).Molecular medicine reports · 2022Article
- Genetic basis of cardiovascular aging is at the core of human longevity.The journal of cardiovascular aging · 2022Article
- TargetingCancers · 2021Review
- [DNMT1 protein promotes retinoblastoma proliferation by silencing MEG3 gene].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Atm deficiency in the DNA polymerase β null cerebellum results in cerebellar ataxia and Itpr1 reduction associated with alteration of cytosine methylation.Nucleic acids research · 2020Article
- MEG3: an Oncogenic Long Non-coding RNA in Different Cancers.Pathology oncology research : POR · 2019Review
- Genomic Reorganization of Lamin-Associated Domains in Cardiac Myocytes Is Associated With Differential Gene Expression and DNA Methylation in Human Dilated Cardiomyopathy.Circulation research · 2019Article
- Two Proximally Close Priority Candidate Genes for diplopodia-1, an Autosomal Inherited Craniofacial-Limb Syndrome in the Chicken: MRE11 and GPR83.The Journal of heredity · 2019Article
- Epigenetic mechanism and target therapy of UHRF1 protein complex in malignancies.OncoTargets and therapy · 2019Review
- Interaction of the epigenetic integrator UHRF1 with the MYST domain of TIP60 inside the cell.Journal of experimental & clinical cancer research : CR · 2017Article
- ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.Scientific reports · 2017Article
- The RB-IL-6 axis controls self-renewal and endocrine therapy resistance by fine-tuning mitochondrial activity.Oncogene · 2017Article
- Defining, distinguishing and detecting the contribution of heterogeneous methylation to cancer heterogeneity.Seminars in cell & developmental biology · 2017Review
- The Rb binding domain of HPV31 E7 is required to maintain high levels of DNA repair factors in infected cells.Virology · 2017Article
- Structural Analysis of Glycine Sarcosine N-methyltransferase from Methanohalophilus portucalensis Reveals Mechanistic Insights into the Regulation of Methyltransferase Activity.Scientific reports · 2016Article
- Transforming Growth Factor-β1 Increases DNA Methyltransferase 1 and 3a Expression through Distinct Post-transcriptional Mechanisms in Lung Fibroblasts.The Journal of biological chemistry · 2016Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression.
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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.