ArticleToxicological sciences : an official journal of the Society of Toxicology2011
ERK crosstalks with 4EBP1 to activate cyclin D1 translation during quinol-thioether-induced tuberous sclerosis renal cell carcinoma.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 21 citations in OpenAlex.
- Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction.Journal of clinical and translational hepatology · 2026Article
- Inhibition of Retinal Neovascularization by BEZ235: Targeting the Akt/4EBP1/Cyclin D1 Pathway in Endothelial Cells.Investigative ophthalmology & visual science · 2025Article
- Vitamin D in tuberous sclerosis complex-associated tumors.Frontiers in pediatrics · 2024Article
- MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells.Journal of radiation research · 2021Article
- Everolimus induces GAmerican journal of physiology. Cell physiology · 2019Article
- Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats.Clinical and experimental nephrology · 2019Article
- Transcriptional and post-translational modifications of B-Raf in quinol-thioether induced tuberous sclerosis renal cell carcinoma.Molecular carcinogenesis · 2016Article
- Potential role of AKT/mTOR signalling proteins in hairy cell leukaemia: association with BRAF/ERK activation and clinical outcome.Scientific reports · 2016Article
- MAPKs' status at early stages of renal carcinogenesis and tumors induced by ferric nitrilotriacetate.Molecular and cellular biochemistry · 2015Article
- Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development.Virchows Archiv : an international journal of pathology · 2014Article
- S6K in geroconversion.Cell cycle (Georgetown, Tex.) · 2013Article
- MEK drives cyclin D1 hyperelevation during geroconversion.Cell death and differentiation · 2013Article
- Crossing paths in Human Renal Cell Carcinoma (hRCC).International journal of molecular sciences · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase signaling cascades have been implicated in a number of human cancers. The tumor suppressor gene tuberous sclerosis-2 (Tsc-2) functions as a negative regulator of mTOR. Critical proteins in both pathways are activated following treatment of Eker rats (Tsc-2(EK/+)) with the nephrocarcinogen 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ), which also results in loss of the wild-type allele of Tsc-2 in renal preneoplastic lesions and tumors. Western blot analysis of kidney tumors formed following treatment of Tsc-2(EK/+) rats with TGHQ for 8 months revealed increases in B-Raf, Raf-1, pERK, cyclin D1, 4EBP1, and p-4EBP1-Ser65, -Thr70, and -Thr37/46 expression. Similar changes are observed following TGHQ-mediated transformation of primary renal epithelial cells derived from Tsc-2(EK/+) rats (quinol-thioether rat renal epithelial [QTRRE] cells) that are also null for tuberin. These cells exhibit high ERK, B-Raf, and Raf-1 kinase activity and increased expression of all p-4EBP1s and cyclin D1. Treatment of the QTRRE cells with the Raf kinase inhibitor, sorafenib, or the MEK1/2 kinase inhibitor, PD 98059, produced a significant decrease in the protein expression of all p-4EBP1s and cyclin D1. Following siRNA knockdown of Raf-1, Western blot analysis revealed a significant decrease in Raf-1, cyclin D1, and all p-4EBP1 forms noted above. In contrast, siRNA knockdown of B-Raf resulted in a nominal change in these proteins. The data indicate that Raf-1/MEK/ERK participates in crosstalk with 4EBP1, which represents a novel pathway interaction leading to increased protein synthesis, cell growth, and kidney tumor formation.
Indexed as
Identifiers
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.