ArticleGenes & development1998
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling.
Article in Genes & development, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 415 papers.
What it found
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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.
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Who cites it
415 citing papers in PubMed, 923 citations in OpenAlex.
- Tumoral TP53 and/or CDKN2A alterations are not reliable prognostic biomarkers in patients with localized Ewing sarcoma: a report from the Children's Oncology Group.Pediatric blood & cancer · 2015Trial
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Senolytic Interventions Enhance the Anti-metastatic Activity of Chemotherapy in Prostate Cancer.Cancer research · 2026Article
- MAPK-driven MYC/p21 axis controls senescence bypass and BCL-XL dependence in vincristine-resistant rhabdomyosarcoma.iScience · 2026Article
- 3'UTR-directed, kinase-proximal mRNA decay inhibits C/EBPβ phosphorylation/activation to suppress senescence in tumor cells.iScience · 2026Article
- ST6GAL1 Is a Functional Regulator of UVA-Induced Photoaging in Human Dermal Fibroblasts.Cells · 2026Article
- Decoding the Raf-Mek-Erk-Rsk pathway in prostate cancer: from molecular mechanisms to clinical opportunities.British journal of cancer · 2026Review
- p16 Beyond Senescence: Cancer Biology Lessons Applied to Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Review
- Protein phosphatase 2 phosphatase activator (PTPA) promotes oncogene-induced senescence and carboplatin response in human malignant pleural mesothelioma cells.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Exercise rejuvenates bone marrow mesenchymal stem cells associated with the inhibition of inflammatory factors and senescence-related factors.Biochemistry and biophysics reports · 2026Article
- Review
- Constitutively active RAS prolongs Cdc42 signalling, while MAPK signalling is attenuated during fission yeast mating.PLoS genetics · 2026Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance.Cancers · 2026Review
- Impact of RAS-MAPK Pathway Genetic Alterations on Radiotherapy Response in Metastatic Lung Adenocarcinoma.JCO precision oncology · 2025Article
- CBX7 regulates chemotherapy-induced senescence-like growth arrest in multiple myeloma via the ERK/STAT3/PIM1 axis.Journal of translational medicine · 2025Article
- Antimicrobial and Anticancer Activities ofNutrients · 2025Article
- The rise of RAS: how gradual oncogene activation shapes the OIS spectrum.Genes & development · 2025Review
- Suppression of MRPL23 induces cellular senescence in hepatocellular carcinoma by targeting HMGB1.Discover oncology · 2025Article
355 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16(INK4a) tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) induces both p53 and p16, and is required for Ras-induced senescence of normal human fibroblasts. Furthermore, activated MEK permanently arrests primary murine fibroblasts but forces uncontrolled mitogenesis and transformation in cells lacking either p53 or INK4a. The precisely opposite response of normal and immortalized cells to constitutive activation of the MAPK cascade implies that premature senescence acts as a fail-safe mechanism to limit the transforming potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors.
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What OpenQuestion holds
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.