ArticleAging cell2018
The nuclear receptor RXRA controls cellular senescence by regulating calcium signaling.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Exploring Replicative Senescence and Oxidative Stress-Induced Remodelling of Mitochondrial-Associated Membranes in Human Skin Fibroblasts.Biomolecules · 2026Article
- Intercompartmental communication in senescence.FEBS open bio · 2026Review
- TEAD4 and RXRA Regulate the Function of Nucleus Pulposus Cells in Intervertebral Disc Degeneration Via the TNF-α/NF-κB Pathway: An Integrated Analysis of Single-Cell RNA-Seq, Bulk RNA-Seq, and In Vitro Validation.Applied biochemistry and biotechnology · 2026Article
- Study on the mechanism ofAnnals of medicine · 2025Article
- Aerobic Exercise Attenuates Autophagy-Lysosomal Flux Deficits via β2-AR-Mediated ESCRT-III Subunit CHMP4B in Mice With Human MAPT P301L.Aging cell · 2025Article
- CCT196969 inhibits TNBC by targeting the HDAC5/RXRA/ASNS axis to down-regulate asparagine synthesis.Journal of experimental & clinical cancer research : CR · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- NFATc1 facilitates hepatocellular carcinoma progression by regulating the senescence-associated secretory phenotype.Scientific reports · 2025Article
- Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.Autophagy · 2025Article
- Troxerutin Delays Skin Keratinocyte Senescence Induced by Ionizing Radiation Both In Vitro and In Vivo.Journal of cosmetic dermatology · 2025Article
- Multiomic Sequencing Reveals Distinctive Gene Expression and Epigenetic Alterations Associated With Primary Sclerosing Cholangitis Development in Treatment-Naïve Pediatric Ulcerative Colitis.Gastro hep advances · 2025Article
- Quercetin preserves mitochondria-endoplasmic reticulum contact sites improving mitochondrial dynamics in aged myocardial cells.Biogerontology · 2024Article
- Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.Neuro-oncology · 2024Article
- Mitochondrial calcium uniporter promotes kidney aging in mice through inducing mitochondrial calcium-mediated renal tubular cell senescence.Acta pharmacologica Sinica · 2024Article
- DiPPI: A Curated Data Set for Drug-like Molecules in Protein-Protein Interfaces.Journal of chemical information and modeling · 2024Article
- Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- MicroRNAs Regulate CaCells · 2023Article
- Alpha lipoamide inhibits diabetic kidney fibrosis via improving mitochondrial function and regulating RXRα expression and activation.Acta pharmacologica Sinica · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium signaling is emerging as a key pathway controlling cellular senescence, a stable cell proliferation arrest playing a fundamental role in pathophysiological conditions, such as embryonic development, wound healing, cancer, and aging. However, how calcium signaling is regulated is still only partially understood. The inositol 1, 4, 5-trisphosphate receptor type 2 (ITPR2), an endoplasmic reticulum calcium release channel, was recently shown to critically contribute to the implementation of senescence, but how ITPR2 expression is controlled is unclear. To gain insights into the regulation of ITPR2 expression, we performed an siRNA screen targeting 160 transcription factors and epigenetic regulators. Interestingly, we discovered that the retinoid X receptor alpha (RXRA), which belongs to the nuclear receptor family, represses ITPR2 expression and regulates calcium signaling though ITPR2 and the mitochondrial calcium uniporter (MCU). Knockdown of RXRA induces the production of reactive oxygen species (ROS) and DNA damage via the ITPR2-MCU calcium signaling axis and consequently triggers cellular senescence by activating p53, whereas RXRA overexpression decreases DNA damage accumulation and then delays replicative senescence. Altogether, our work sheds light on a novel mechanism controlling calcium signaling and cellular senescence and provides new insights into the role of nuclear receptors.
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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.