ArticleBMC genomics2011
An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence.
Article in BMC genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Is Cellular Senescence a Biological Feature of Long COVID? A Transcriptomic Analysis Across Comparative Postacute Sequelae Phenotypes.The Journal of infectious diseases · 2026Article
- The Relationship Between Immunogenic Cell Death and Cellular Senescence in Cancer Immunotherapy.Life (Basel, Switzerland) · 2026Review
- Anti-Müllerian hormone induces a reversible quiescence-associated secretory phenotype in preantral follicles†.Biology of reproduction · 2026Article
- Heterogeneity of Cellular Senescence: Subtype-Specific Mechanisms and the Emerging Role of Plasma Membrane Damage.Cancer science · 2025Review
- The impacts of chronic infections on shaping cellular senescence.Immunity & ageing : I & A · 2025Review
- Investigating the ageing-Parkinson's disease nexus: standardisation of in vitro models and techniques by the PD-AGE network.NPJ Parkinson's disease · 2025Review
- Targeting immunosenesence promotes clearance of senescent cells.Immunity & ageing : I & A · 2025Review
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- Layilin: a multifunctional hyaluronan receptor in physiology and pathology.Frontiers in oncology · 2025Review
- Emerging Landscape of Mesenchymal Stem Cell Senescence Mechanisms and Implications on Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Prevention of UVB-Induced Photoaging by an Ethyl Acetate Fraction fromInternational journal of molecular sciences · 2024Article
- Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Cell communication and signaling : CCS · 2024Article
- Identification of potential drug targets for allergic diseases from a genetic perspective: A mendelian randomization study.Clinical and translational allergy · 2024Article
- Comprehensive landscape of the miRNA-regulated prognostic marker LAYN with immune infiltration and stemness in pan-cancer.Journal of cancer research and clinical oncology · 2023Article
- Overexpression of adrenomedullin (ADM) alleviates the senescence of human dental pulp stem cells by regulating the miR-152/CCNA2 pathway.Cell cycle (Georgetown, Tex.) · 2023Article
- Systematic estimation of biological age ofFrontiers in aging · 2023Article
- Establishment of In Vitro Models by Stress-Induced Premature Senescence for Characterizing the Stromal Vascular Niche in Human Adipose Tissue.Life (Basel, Switzerland) · 2022Article
- Rad54L promotes bladder cancer progression by regulating cell cycle and cell senescence.Medical oncology (Northwood, London, England) · 2022Article
- Genetic Regulation of DNA Methylation Yields Novel Discoveries in GWAS of Colorectal Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- p27, The Cell Cycle and Alzheimer´s Disease.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCellular senescence is an irreversible cell cycle arrest that normal cells undergo in response to progressive shortening of telomeres, changes in telomeric structure, oncogene activation or oxidative stress and acts as an important tumour suppressor mechanism.
resultsTo identify the downstream effectors of the p53-p21 and p16-pRB tumour suppressor pathways crucial for mediating entry into senescence, we have carried out a loss-of-function RNA interference screen in conditionally immortalised human fibroblasts that can be induced to rapidly undergo senescence, whereas in primary cultures senescence is stochastic and occurs asynchronously. These cells are immortal but undergo a rapid irreversible arrest upon activation of the p53-p21 and p16-pRB pathways that can be readily bypassed upon their inactivation. The primary screen identified 112 known genes including p53 and another 29 shRNAmirs targetting as yet unidentified loci. Comparison of these known targets with genes known to be up-regulated upon senescence in these cells, by micro-array expression profiling, identified 4 common genes TMEM9B, ATXN10, LAYN and LTBP2/3. Direct silencing of these common genes, using lentiviral shRNAmirs, bypassed senescence in the conditionally immortalised cells.
conclusionThe senescence bypass screen identified TMEM9B, ATXN10, LAYN and LTBP2/3 as novel downstream effectors of the p53-p21 and p16-pRB tumour suppressor pathways. Although none of them has previously been linked to cellular senescence, TMEM9B has been suggested to be an upstream activator of NF-κB signalling which has been found to have a causal role in promoting senescence. Future studies will focus on determining on how many of the other primary hits also have a casual role in senescence and what is the mechanism of action.
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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.