ArticleProceedings of the National Academy of Sciences of the United States of America2019
Repression of eEF2K transcription by NF-κB tunes translation elongation to inflammation and dsDNA-sensing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- Down-regulation of GPRC5A Confers Protection Against Periodontitis.Inflammation · 2026Article
- Evaluation of annexin A1, carbonic anhydrase 1, and elongation factor 1-gamma levels in periodontal diseases.BMC oral health · 2025Article
- Article
- eEF-2K Deficiency Boosts the Virus-Specific Effector CD8Viruses · 2024Article
- Elongation factor 2 in cancer: a promising therapeutic target in protein translation.Cellular & molecular biology letters · 2024Review
- ANKRD1 expression is aberrantly upregulated in the mdm mouse model of muscular dystrophy and induced by stretch through NFκB.Journal of muscle research and cell motility · 2024Article
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.bioRxiv : the preprint server for biology · 2024Article
- IL-6 translation is a therapeutic target of human cytokine release syndrome.The Journal of experimental medicine · 2023Article
- Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.Cancer cell · 2023Article
- Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells.Experimental and therapeutic medicine · 2023Article
- Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System.Biomedicines · 2022Review
- Analysis of senescence-responsive stress fiber proteome reveals reorganization of stress fibers mediated by elongation factor eEF2 in HFF-1 cells.Molecular biology of the cell · 2022Article
- Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis.Frontiers in pharmacology · 2020Article
- Integrated analysis of immune-related genes in endometrial carcinoma.Cancer cell international · 2020Article
- Disease Activity-Associated Alteration of mRNA mFrontiers in cell and developmental biology · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Gene expression is rapidly remodeled by infection and inflammation in part via transcription factor NF-κB activation and regulated protein synthesis. While protein synthesis is largely controlled by mRNA translation initiation, whether cellular translation elongation factors are responsive to inflammation and infection remains poorly understood. Here, we reveal a surprising mechanism whereby NF-κB restricts phosphorylation of the critical translation elongation factor eEF2, which catalyzes the protein synthesis translocation step. Upon exposure to NF-κB-activating stimuli, including TNFα, human cytomegalovirus infection, or double-stranded DNA, eEF2 phosphorylation on Thr56, which slows elongation to limit protein synthesis, and the overall abundance of eEF2 kinase (eEF2K) are reduced. Significantly, this reflected a p65 NF-κB subunit-dependent reduction in eEF2K pre-mRNA, indicating that NF-κB activation represses eEF2K transcription to decrease eEF2K protein levels. Finally, we demonstrate that reducing eEF2K abundance regulates protein synthesis in response to a bacterial toxin that inactivates eEF2. This establishes that NF-κB activation by diverse physiological effectors controls eEF2 activity via a transcriptional repression mechanism that reduces eEF2K polypeptide abundance to preclude eEF2 phosphorylation, thereby stimulating translation elongation and protein synthesis. Moreover, it illustrates how nuclear transcription regulation shapes translation elongation factor activity and exposes how eEF2 is integrated into innate immune response networks orchestrated by NF-κB.
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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.