ArticleCell death and differentiation2015
JMJD3 promotes SAHF formation in senescent WI38 cells by triggering an interplay between demethylation and phosphorylation of RB protein.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- Heat inducible nuclear translocation of Kdm6bb drives temperature dependent sex reversal in Nile tilapia.PLoS genetics · 2025Article
- Discovery and structural studies of histone demethylases.Frontiers in epigenetics and epigenomics · 2025Review
- JMJD3 deficiency disturbs dopamine biosynthesis in midbrain and aggravates chronic inflammatory pain.Acta neuropathologica communications · 2024Article
- P16iScience · 2024Article
- A Mesenchymal stem cell Aging Framework, from Mechanisms to Strategies.Stem cell reviews and reports · 2024Review
- Review
- Korean Red Ginseng Attenuates Particulate Matter-Induced Senescence of Skin Keratinocytes.Antioxidants (Basel, Switzerland) · 2023Article
- Regulation of intrinsic and extrinsic metabolic pathways in tumour-associated macrophages.The FEBS journal · 2023Review
- A Novel Aging-Related Prognostic lncRNA Signature Correlated with Immune Cell Infiltration and Response to Immunotherapy in Breast Cancer.Molecules (Basel, Switzerland) · 2023Article
- Anti-hsa-miR-59 alleviates premature senescence associated with Hutchinson-Gilford progeria syndrome in mice.The EMBO journal · 2023Article
- Context-Dependent Functions of KDM6 Lysine Demethylases in Physiology and Disease.Advances in experimental medicine and biology · 2023Article
- Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis.Frontiers in immunology · 2023Article
- Establishment and validation of an aging-related risk signature associated with prognosis and tumor immune microenvironment in breast cancer.European journal of medical research · 2022Article
- Targeting cellular senescence to combat cancer and ageing.Molecular oncology · 2022Review
- Post-translational modifications on the retinoblastoma protein.Journal of biomedical science · 2022Review
- Epigenetic Regulation of Cellular Senescence.Cells · 2022Review
- EZH2-CCF-cGAS Axis Promotes Breast Cancer Metastasis.International journal of molecular sciences · 2022Article
- Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary human fibroblasts undergoing oncogene-induced or replicative senescence are known to form senescence-associated heterochromatin foci (SAHF), which can stabilize the state of senescence. The retinoblastoma (RB) protein has an important role in SAHF; cells that lack active RB pathway fail to form SAHF. It has been known that the posttranslational modifications of RB, for example, phosphorylation, regulate its function. To date, whether methylation of RB impacts on the SAHF formation is unknown. Here we report that JMJD3, a histone demethylase catalyzing the tri-methylation of H3K27 (H3K27me3), can demethylate the non-histone protein RB at the lysine810 residue (K810), which is a target of the methyltransferase Set7/9. We detected a significant upregulation of JMJD3 during cellular senescence and SAHF formation in WI38 cells induced by H-RasV(12), and we found that ectopic expression of JMJD3 promoted cellular senescence and SAHF formation in WI38 cells. Furthermore, during the process of SAHF assembly, JMJD3 was transported to the cytoplasm and interacted with RB through its demethylase domain JmjC. Significantly, our data demonstrated that the JMJD3-mediated demethylation of RB at K810 impeded the interaction of RB with the protein kinase CDK4 and resulted in reduced level of phosphorylation of RB at Serine807/811 (S807/811), implicating an important role of the interplay between the demethylation and phosphorylation of RB in SAHF assembly. This study highlights the role of JMJD3 as a novel inducer of SAHF formation through demethylating RB and provides new insights into the mechanisms of cellular senescence and SAHF assembly.
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