ArticleCell cycle (Georgetown, Tex.)2018
Perturbation of RNA Polymerase I transcription machinery by ablation of HEATR1 triggers the RPL5/RPL11-MDM2-p53 ribosome biogenesis stress checkpoint pathway in human cells.
Article in Cell cycle (Georgetown, Tex.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 44 citations in OpenAlex.
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- Long-Term Heat Stress Triggers Immune Activation and Cell Death Remodeling in the Brain of Largemouth Bass (Animals : an open access journal from MDPI · 2025Article
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- Mechanisms of ribosomopathy and phase separation-related ribosomopathy.Journal of Zhejiang University. Science. B · 2025Review
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- ETS1-Driven Nucleolar Stress Orchestrates OLR1Human mutation · 2025Article
- Discovering Root Causal Genes with High Throughput Perturbations.bioRxiv : the preprint server for biology · 2024Article
- Revealing the potential role of hub metabolism-related genes and their correlation with immune cells in acute ischemic stroke.IET systems biology · 2024Article
- Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.EMBO reports · 2024Article
- The Effects of Deregulated Ribosomal Biogenesis in Cancer.Biomolecules · 2023Review
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- Organ-specific host differential gene expression analysis in systemic candidiasis: A systems biology approach.Microbial pathogenesis · 2022Article
- Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways.Nature communications · 2022Article
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Review
- A high-throughput assay for directly monitoring nucleolar rRNA biogenesis.Open biology · 2022Article
- Silencing Ribosomal Protein L22 Promotes Proliferation and Migration, and Inhibits Apoptosis of Gastric Cancer Cells by Regulating the Murine Double Minute 2-Protein 53 (MDM2-p53) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Loss of BRMS2 induces cell growth inhibition and translation capacity reduction in colorectal cancer cells.American journal of cancer research · 2021Article
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5 authors at 2 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Ribosome biogenesis is an energy consuming process which takes place mainly in the nucleolus. By producing ribosomes to fuel protein synthesis, it is tightly connected with cell growth and cell cycle control. Perturbation of ribosome biogenesis leads to the activation of p53 tumor suppressor protein promoting processes like cell cycle arrest, apoptosis or senescence. This ribosome biogenesis stress pathway activates p53 through sequestration of MDM2 by a subset of ribosomal proteins (RPs), thereby stabilizing p53. Here, we identify human HEATR1, as a nucleolar protein which positively regulates ribosomal RNA (rRNA) synthesis. Downregulation of HEATR1 resulted in cell cycle arrest in a manner dependent on p53. Moreover, depletion of HEATR1 also caused disruption of nucleolar structure and activated the ribosomal biogenesis stress pathway - RPL5 / RPL11 dependent stabilization and activation of p53. These findings reveal an important role for HEATR1 in ribosome biogenesis and further support the concept that perturbation of ribosome biosynthesis results in p53-dependent cell cycle checkpoint activation, with implications for human pathologies including cancer.
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