ArticleEMBO reports2003
Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts.
Article in EMBO reports, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence.Aging cell · 2025Article
- The Matrix Protein Tropoelastin Prolongs Mesenchymal Stromal Cell Vitality and Delays Senescence During Replicative Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A novel role of Fas in delaying cellular senescence.Heliyon · 2023Article
- TElomeric repeat-containing RNA (TERRA): Physiological functions and relevance in cancer.Frontiers in oncology · 2022Review
- Mechanisms and Regulation of Cellular Senescence.International journal of molecular sciences · 2021Review
- The Paradoxical Role of Cellular Senescence in Cancer.Frontiers in cell and developmental biology · 2021Review
- Hepatic senescence, the good and the bad.World journal of gastroenterology · 2019Review
- Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells.Molecular carcinogenesis · 2019Article
- CD46 knock-out using CRISPR/Cas9 editing of hTERT immortalized human cells modulates complement activation.PloS one · 2019Article
- The Regulation of Cellular Functions by the p53 Protein: Cellular Senescence.Cold Spring Harbor perspectives in medicine · 2017Review
- Cellular senescence: a hitchhiker's guide.Human cell · 2015Review
- Senescence from G2 arrest, revisited.Cell cycle (Georgetown, Tex.) · 2015Review
- Purinergic P2Y₁₄ receptor modulates stress-induced hematopoietic stem/progenitor cell senescence.The Journal of clinical investigation · 2014Article
- Defining the toxicology of aging.Trends in molecular medicine · 2014Review
- Cellular Senescence - its role in cancer and the response to ionizing radiation.Genome integrity · 2011Article
- Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells.Oncotarget · 2011Article
- Regulation of senescence in cancer and aging.Journal of aging research · 2011Article
- Ras-induced senescence and its physiological relevance in cancer.Current cancer drug targets · 2010Review
- Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.BMC genomics · 2010Article
- The relative contributions of the p53 and pRb pathways in oncogene-induced melanocyte senescence.Aging · 2009Article
Corrections and comments
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5 authors.
Funding
Abstract
Current models envision replicative senescence to be under dual control by the p53 and retinoblastoma (RB) tumour-suppressor pathways. The role of the p16(INK4a)-RB pathway is controversial, and the function of RB in human cells has not been tested directly. We used targeted homologous recombination to knock out one copy of RB in presenescent human fibroblasts. During entry into senescence, RB+/- cells underwent spontaneous loss of heterozygosity and the resultant RB-/- clones bypassed senescence. The extended lifespan phase was eventually terminated by a crisis-like state. The same phenotype was documented for p21(CIP1/WAF1) and p53 heterozygous cells, indicating that loss of function of all three genes results in failure to establish senescence. By contrast, the abolition of p16 function by the expression of a p16-insensitive cyclin-dependent kinase 4 protein or siRNA-mediated knockdown provided only minimal lifespan extension that was terminated by senescence. We propose that p53, p21 and RB act in a linear genetic pathway to regulate cell entry into replicative senescence.
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