ArticleMolecular cell2016
Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced Phospho-Regulatory Circuit.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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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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
55 citing papers in PubMed, 116 citations in OpenAlex.
- Rigosertib Reverses Hypertrophic Cardiomyopathy in Noonan Syndrome.Circulation · 2026Article
- Systematic Analysis of MRTFB Phosphoproteomic Datasets Reveals Co-Regulated Kinase Networks and Co-Occurring Phosphosites Associated with the Actin Cytoskeleton Pathway.Current issues in molecular biology · 2026Article
- Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer.Journal of advanced research · 2025Article
- PGRP-S promotes hepatocellular carcinoma progression via MAPK/ERK pathway by interaction with TTC1.Scientific reports · 2025Article
- CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses.iScience · 2025Article
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- Article
- HOXB7 drives bladder cancer progression via H-Ras/ERK signaling: a potential therapeutic target and prognostic biomarker.Frontiers in oncology · 2025Article
- Advances in the role of the IGF signaling system in myelodysplastic syndromes and acute myeloid leukemia.Frontiers in oncology · 2025Review
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy.JCI insight · 2024Article
- Article
- Review
- Multiplexed imaging for probing RAS-RAF interactions in living cells.Biochimica et biophysica acta. Biomembranes · 2023Article
- RAS degraders: The new frontier for RAS-driven cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation.International journal of molecular sciences · 2023Review
- Selected Approaches to Disrupting Protein-Protein Interactions within the MAPK/RAS Pathway.International journal of molecular sciences · 2023Review
- Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na).Pharmaceutics · 2023Review
- Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent.International journal of molecular sciences · 2023Article
- Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer cell international · 2022Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Ras pathway signaling plays a critical role in cell growth control and is often upregulated in human cancer. The Raf kinases selectively interact with GTP-bound Ras and are important effectors of Ras signaling, functioning as the initiating kinases in the ERK cascade. Here, we identify a route for the phospho-inhibition of Ras/Raf/MEK/ERK pathway signaling that is mediated by the stress-activated JNK cascade. We find that key Ras pathway components, the RasGEF Sos1 and the Rafs, are phosphorylated on multiple S/TP sites in response to JNK activation and that the hyperphosphorylation of these sites renders the Rafs and Sos1 unresponsive to upstream signals. This phospho-regulatory circuit is engaged by cancer therapeutics, such as rigosertib and paclitaxel/Taxol, that activate JNK through mitotic and oxidative stress as well as by physiological regulators of the JNK cascade and may function as a signaling checkpoint to suppress the Ras pathway during conditions of cellular stress.
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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.