ArticleGenes & development2013
Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 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.
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.
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Who cites it
114 citing papers in PubMed, 190 citations in OpenAlex.
- Junctional plakoglobin regulates intestinal epithelial cell proliferation via MAPK/ERK signaling.Cell communication and signaling : CCS · 2026Article
- Review
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- ID2 Suppresses Multiple Myeloma Cell Proliferation by Repressing the Activity of the Transcription Factor TCF3.Blood cancer discovery · 2026Article
- Abrogation of aberrant glycolytic interactions eliminates senescent cells and alleviates aging-related dysfunctions.Signal transduction and targeted therapy · 2025Article
- Tumor-derived extracellular vesicles: Bridging communication and next-generation theranostics.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Nanotoxicity of Porous Silica Nanoparticles: Physicochemical Properties and Mechanistic Cellular Endpoints.Nanomaterials (Basel, Switzerland) · 2025Review
- CBX7 regulates chemotherapy-induced senescence-like growth arrest in multiple myeloma via the ERK/STAT3/PIM1 axis.Journal of translational medicine · 2025Article
- Balancing senescence and apoptosis: therapeutic insights into aging and cancer.Molecular and cellular biochemistry · 2025Review
- Cells of all trades - on the importance of spatial positioning of senescent cells in development, healing and aging.FEBS letters · 2025Review
- Role of Cellular Senescence in Parkinson's Disease: Potential for Disease-Modification Through Senotherapy.Biomedicines · 2025Review
- Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Identification and validation of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration.Frontiers in immunology · 2025Article
- The potential of flavonoids to mitigate cellular senescence in cardiovascular disease.Biogerontology · 2024Review
- 10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically.Nature communications · 2024Article
- Senescent Macrophages Release Inflammatory Cytokines and RNA-Loaded Extracellular Vesicles to Circumvent Fibroblast Senescence.Biomedicines · 2024Article
- Review
- A guide to ERK dynamics, part 2: downstream decoding.The Biochemical journal · 2023Article
- Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.Cell cycle (Georgetown, Tex.) · 2023Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Constitutive activation of growth factor signaling pathways paradoxically triggers a cell cycle arrest known as cellular senescence. In primary cells expressing oncogenic ras, this mechanism effectively prevents cell transformation. Surprisingly, attenuation of ERK/MAP kinase signaling by genetic inactivation of Erk2, RNAi-mediated knockdown of ERK1 or ERK2, or MEK inhibitors prevented the activation of the senescence mechanism, allowing oncogenic ras to transform primary cells. Mechanistically, ERK-mediated senescence involved the proteasome-dependent degradation of proteins required for cell cycle progression, mitochondrial functions, cell migration, RNA metabolism, and cell signaling. This senescence-associated protein degradation (SAPD) was observed not only in cells expressing ectopic ras, but also in cells that senesced due to short telomeres. Individual RNAi-mediated inactivation of SAPD targets was sufficient to restore senescence in cells transformed by oncogenic ras or trigger senescence in normal cells. Conversely, the anti-senescence viral oncoproteins E1A, E6, and E7 prevented SAPD. In human prostate neoplasms, high levels of phosphorylated ERK were found in benign lesions, correlating with other senescence markers and low levels of STAT3, one of the SAPD targets. We thus identified a mechanism that links aberrant activation of growth signaling pathways and short telomeres to protein degradation and cellular senescence.
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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.