ArticleCellular signalling2015
ERK1/2 can feedback-regulate cellular MEK1/2 levels.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 27 citations in OpenAlex.
- Genetic Regulation of ERK1/2-c-Fos Signalling Pathway in Newcastle Disease Virus-Induced Apoptosis of Human Pancreatic Cancer Stem Cells.The Malaysian journal of medical sciences : MJMS · 2026Article
- Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.Biomedicines · 2024Review
- Article
- MEK inhibitors for the treatment of non-small cell lung cancer.Journal of hematology & oncology · 2021Review
- Growth Inhibitory Signaling of the Raf/MEK/ERK Pathway.International journal of molecular sciences · 2020Review
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- Tubeimoside I Inhibits Cell Proliferation and Induces a Partly Disrupted and Cytoprotective Autophagy Through Rapidly Hyperactivation of MEK1/2-ERK1/2 Cascade via Promoting PTP1B in Melanoma.Frontiers in cell and developmental biology · 2020Article
- Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly.BMC cancer · 2019Article
- Targeting ERK beyond the boundaries of the kinase active site in melanoma.Molecular carcinogenesis · 2019Review
- Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression.International journal of molecular sciences · 2019Review
- Transcriptional Response of White Adipose Tissue to Withdrawal of Vitamin B3.Molecular nutrition & food research · 2019Article
- Biological Rationale for Targeting MEK/ERK Pathways in Anti-Cancer Therapy and to Potentiate Tumour Responses to Radiation.International journal of molecular sciences · 2019Review
- A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses.Cellular signalling · 2018Article
- Steady-State Levels of Phosphorylated Mitogen-Activated Protein Kinase Kinase 1/2 Determined by Mortalin/HSPA9 and Protein Phosphatase 1 Alpha inMolecular and cellular biology · 2017Article
- Regulation of BRAF protein stability by a negative feedback loop involving the MEK-ERK pathway but not the FBXW7 tumour suppressor.Cellular signalling · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Signal transduction of the Raf/MEK/ERK pathway is regulated by various feedback mechanisms. Given the greater molar ratio between Raf-MEK than between MEK-ERK in cells, it may be possible that MEK1/2 levels are regulated to modulate Raf/MEK/ERK activity upon pathway stimulation. Nevertheless, it has not been reported whether MEK1/2 expression can be subject to a feedback regulation. Here, we report that the Raf/MEK/ERK pathway can feedback-regulate cellular MEK1 and MEK2 levels. In different cell types, ΔRaf-1:ER- or B-Raf(V600E)-mediated MEK/ERK activation increased MEK1 but decreased MEK2 levels. These regulations were abrogated by ERK1/2 knockdown mediated by RNA interference, suggesting the presence of a feedback mechanism that regulates MEK1/2 levels. Subsequently, analyses using qPCR and luciferase reporters of the DNA promoter and 3' untranslated region revealed that the feedback MEK1 upregulation was in part attributed to increased transcription. However, the feedback MEK2 downregulation was only observed at protein levels, which was blocked by the proteasome inhibitors, MG132 and bortezomib, suggesting that the MEK2 regulation is mediated at a post-translational level. These results suggest that the Raf/MEK/ERK pathway can feedback-regulate cellular levels of MEK1 and MEK2, wherein MEK1 levels are upregulated at transcriptional level whereas MEK2 levels are downregulated at posttranslational level.
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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.