ArticleOncogene2012
Parallel pathways in RAF-induced senescence and conditions for its reversion.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
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- RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation.Nature communications · 2022Article
- Innate immunity mediator STING modulates nascent DNA metabolism at stalled forks in human cells.Frontiers in molecular biosciences · 2022Article
- A protocol to quantify chromatin compaction with confocal and super-resolution microscopy in cultured cells.STAR protocols · 2021Article
- Ouabain and chloroquine trigger senolysis of BRAF-V600E-induced senescent cells by targeting autophagy.Aging cell · 2021Article
- H2B Type 1-K Accumulates in Senescent Fibroblasts with Persistent DNA Damage along with Methylated and Phosphorylated Forms of HMGA1.Proteomes · 2021Article
- Reduced RNA turnover as a driver of cellular senescence.Life science alliance · 2021Article
- CircularRNA biology · 2021Article
- Functional heterogeneity in senescence.Biochemical Society transactions · 2020Review
- 4D Genome Rewiring during Oncogene-Induced and Replicative Senescence.Molecular cell · 2020Article
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- Integrated analysis of H2A.Z isoforms function reveals a complex interplay in gene regulation.eLife · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We developed a clonal WI-38hTERT/GFP-RAF1-ER immortal cell line to study RAF-induced senescence of human fibroblasts. Activation of the GFP-RAF1-ER kinase by addition of 4-hydroxy-tamoxifen led to a robust induction of senescence within one population doubling, accompanied by the assembly of heterochromatic foci. At least two pathways contribute in parallel to this senescence leading to the accumulation of p15, p16, p21 and p27 inhibitors of cyclin-dependent kinases (CKIs). Cells that traversed S phase after RAF1 kinase activation experienced a replicative stress manifested by phosphorylation of H2AX and Chk2 and synthesis of p21. However, about half the cells in the population were blocked without passing through S phase and did not show activation of DNA-damage checkpoints. When the cells were cultivated in 5% oxygen, RAF1 activation generated minimal reactive oxygen species, but RAF-induced senescence occurred efficiently in these conditions even in the presence of anti-oxidants or inhibitors of DNA checkpoint pathways. Despite the presence of heterochromatic foci, simultaneous knockdown of p16 and p21 with inactivation of the GFP-RAF1-ER kinase led to rapid reversion of the senescent state with the majority of cells becoming competent for long-term proliferation. These results demonstrate that replicative and oxidative stresses are not required for RAF-induced senescence, and this senescence is readily reversed upon loss of CKIs.
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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.