ArticleCellular and molecular life sciences : CMLS2021
Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome.Molecular psychiatry · 2026Article
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- MiR-125b targeted regulation of MKNK2 inhibits multiple myeloma proliferation and invasion.American journal of translational research · 2024Article
- Dissecting the effects of METTL3 on alternative splicing in prostate cancer.Frontiers in oncology · 2023Article
- MNK Proteins as Therapeutic Targets in Leukemia.OncoTargets and therapy · 2023Review
- LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2.Cell death & disease · 2022Article
- Therapeutic overexpression of miR-92a-2-5p ameliorated cardiomyocyte oxidative stress injury in the development of diabetic cardiomyopathy.Cellular & molecular biology letters · 2022Article
- Review
- SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain.Pharmacological reviews · 2021Review
- Identification of miRNA-Mediated Subpathways as Prostate Cancer Biomarkers Based on Topological Inference in a Machine Learning Process Using Integrated Gene and miRNA Expression Data.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
eIF4E plays key roles in protein synthesis and tumorigenesis. It is phosphorylated by the kinases MNK1 and MNK2. Binding of MNKs to eIF4G enhances their ability to phosphorylate eIF4E. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G. These effects provide a novel mechanism by which mTORC1 signaling impairs the function of MNK2 and thereby decreases eIF4E phosphorylation. MNK2[S74A] knock-in cells show enhanced phosphorylation of eIF4E and S6K1 (i.e., increased mTORC1 signaling), enlarged cell size, and increased invasive and transformative capacities. MNK2[Ser74] phosphorylation was inversely correlated with disease progression in human prostate tumors. MNK inhibition exerted anti-proliferative effects in prostate cancer cells in vitro. These findings define a novel feedback loop whereby mTORC1 represses MNK2 activity and oncogenic signaling through eIF4E phosphorylation, allowing reciprocal regulation of these two oncogenic pathways.
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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.