Ask about this productRelated genes to: EEF2 antibody
- Gene:
- EEF2 NIH gene
- Name:
- eukaryotic translation elongation factor 2
- Previous symbol:
- EF2
- Synonyms:
- EEF-2
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1991-03-11
- Date modifiied:
- 2015-09-11
Related products to: EEF2 antibody
Related articles to: EEF2 antibody
- Skeletal muscle is the largest organ by mass in the human body, and its functional capacity depends on the precise coordination of protein synthesis, mitochondrial bioenergetics, and regenerative potential. Eukaryotic translation initiation factor 3 (eIF3), a 13-subunit complex (~800 kDa) best known for its multifaceted roles in cancer, is now emerging as a key translational regulator in skeletal muscle physiology and disease. Here, we present a perspective that synthesizes recent advances into a unifying "dual-phase guardian" model. In the first phase, eIF3f acts at the level of translation initiation as a scaffold bridging mTORC1 and S6K1, integrating anabolic and catabolic signals, particularly the MAFbx/Atrogin-1 ubiquitin-proteasome axis, to govern net protein synthesis and muscle mass. In the second phase, eIF3e remains bound to 80S ribosomes during early translation elongation (codons 1-60) of approximately 2700 mRNAs encoding mitochondrial and membrane-associated proteins, facilitating co-translational quality control through chaperone recruitment (e.g., CCT/TRiC). Haploinsufficiency of eIF3e in mice produces mitochondrial hyperfusion, diminished respiratory complex I activity, sarcomeric degeneration, and progressive loss of grip strength, a phenotype recapitulating features of mitochondrial myopathy. Complementing these findings, eIF3b supports satellite cell-mediated muscle regeneration by resolving RNA G-quadruplex structures in the 5'-UTR of Anp32e mRNA, while eIF3a modulates fibrotic remodeling through TGF-β/Smad3 signaling. We situate these subunit-level findings within the broader landscape of translational regulators in muscle (eIF2α/ISR, eIF5A, eEF2) and critically evaluate the translational potential and therapeutic challenges, including the absence of human clinical data, tissue-selectivity concerns, and species-specific limitations, that must be addressed before these mechanistic insights can inform treatment of sarcopenia, disuse atrophy, and mitochondrial myopathy. - Source: PubMed
Xia JianingLiao KexinWang JiahuanLu MinghaoMu YonghaoLin Yingying - Polyglutamine-binding protein 1 (PQBP1) has emerged as a multifaceted regulator of gene expression, acting not only in the nucleus to influence transcription and splicing but also in the cytoplasm to control protein synthesis. A recent discovery identified a direct interaction between PQBP1 and the translation elongation factor eEF2, unveiling a new checkpoint in the elongation phase of protein synthesis. PQBP1 binds preferentially to the non-phosphorylated form of eEF2 and protects it from phosphorylation at Thr56 by its kinase eEF2K. Through this mechanism, PQBP1 promotes continuous elongation under conditions where unchecked eEF2K activity would otherwise stall ribosomes. The PQBP1-eEF2 complex plays critical roles in maintaining global proteome homeostasis and enabling activity-dependent protein synthesis in neurons. Disruption of this protein-protein interaction (PPI), whether by genetic mutations in PQBP1 or by sequestration of PQBP1 in cellular aggregates, has been linked to pathological states ranging from intellectual disability and impaired synaptic plasticity to altered innate immune responses and possibly tumorigenesis. In this review, we summarize the current understanding of the PQBP1-eEF2 interaction, its structural basis and regulation, the physiological processes it governs, and the consequences of its disruption in disease. We also discuss therapeutic considerations - when stabilizing this interaction might be beneficial (e.g. to restore synaptic function in neurodegeneration) versus when inhibiting it could be advantageous (e.g. to dampen excessive translation in cancer). Finally, we highlight experimental strategies and open questions for future research on this newly recognized nexus of translation control. - Source: PubMed
Publication date: 2026/04/02
Kamel Emadeldin MKhadrawy Sally MostafaAli Mohamed A MAhmed Noha AYassin Nour Y SAlkhedhairi SalehAlkhayl Faris F AbaLamsabhi Al Mokhtar - Significant genetic heterogeneity has hindered the identification of molecular targets and development of effective targeted therapies for triple negative breast cancer. Currently available targeted therapies are not curative for TNBC patients. Eukaryotic Elongation Factor-2 kinase (eEF2K) is a clinically significant proto-oncogenic therapeutic target linking this atypical alpha kinase to poor patient survival and a key driver of tumor growth and progression in TNBC, positioning it as a critical and emerging molecular target. Development of eEF2K inhibitors for clinical translation has been challenging due to the unknown three-dimensional structure and lack of potent and selective eEF2K inhibitors. Here, we employed a homology modeling, in silico physics-based molecular simulations studies to rationally design, synthesize and in vitro and in vivo identification a novel potent eEF2K inhibitor. The lead compound-2I demonstrated a potential to engage in covalent interactions with eEF2K enzyme, as suggested by in silico covalent docking and static interaction analyses, and significant in vitro inhibitory activity and suppressed primary and multidrug resistant TNBC cell proliferation at submicromolar concentrations, induced ferroptosis and apoptosis, while having no impact on normal breast epithelial cells. In vivo systemic injection of the eEF2K inhibitor encapsulated in single-lipid nanoparticles demonstrated remarkable therapeutic efficacy and suppressing tumor growth in multiple orthotopic TNBC xenograft models in mice with no sign of toxicity. eEF2K inhibition synergistically enhanced the efficacy of standard chemotherapeutics such as paclitaxel. Our results indicate that the novel eEF2K-targeted nanotherapy is safe and has a significant potential for clinical translation as a monotherapy or in combination with chemotherapy for treatment of patients with TNBC or other eEF2K-dependent solid cancers. - Source: PubMed
Publication date: 2026/04/06
Onder Ferah ComertKahraman NerminSiyah PinarDurdağı SerdarAtici Esen BellurAtalay PinarDilmac SayraOzyurt RumeysaKara GoknurGul OgunFokt IzabelaPriebe WaldemarGuzel MustafaAy MehmetOzpolat Bulent - This study aims to enhance milk production and quality in dairy cows. Using cultured MAC-T cells as a model, it seeks to investigate the effects of valine, lysine, and threonine, as well as their optimal combinations, on the synthesis of α-casein by MAC-T cells. Following a 12-h serum starvation period, MAC-T cells were supplemented with varying concentrations of each amino acid individually. The appropriate concentration ranges and optimal levels for valine, lysine, and threonine were determined using ELISA. Response surface methodology was employed to identify the optimal combination of the three amino acids. The resulting α-casein synthesis in the combined treatment group (MIX group) was then compared with that achieved at the individual optimal concentrations and validated by ELISA. Furthermore, mRNA expression levels of the α-casein-encoding gene and key components of the mTOR signaling pathway were analyzed by RT-qPCR, while protein phosphorylation levels were assessed via Western blot. To confirm the functional involvement of the mTOR pathway, a rapamycin-based inhibition assay was conducted. The maximal stimulation of α-casein synthesis in MAC-T cells was observed at valine, lysine, and threonine concentrations of 4 × Val (25.528 mmol/L), 1 × Lys (7.364 mmol/L), and 0.5 × Thr (1.473 mmol/L), respectively. The optimal amino acid combination (MIX) was determined to be valine:lysine:threonine = 36.114:9.027:4.602 mmol/L. α-Casein synthesis in the MIX group was significantly higher than in any individual amino acid supplementation group ( < 0.01). Supplementation with the MIX medium markedly upregulated the relative mRNA expression of α-casein encoding genes ( and ) and key components of the mTOR signaling pathway (, , , , , , , , and ), as well as enhanced the phosphorylation levels of mTOR pathway-related proteins (mTOR, S6K1, 4EBP1, RPS6, and eEF2) ( < 0.01). Treatment with rapamycin significantly suppressed the mRNA expression of these genes, reduced protein phosphorylation, and inhibited α-casein synthesis ( < 0.01); however, co-supplementation with the optimal amino acid combination partially alleviated this suppression, indicating a protective regulatory role of the MIX formulation. The optimal combination of valine, lysine, and threonine was determined to be 36.114:9.027:4.602 mmol/L, corresponding to an approximate molar ratio of 8:2:1. This specific ratio significantly promotes α-casein synthesis in MAC-T cells through activation of the mTOR signaling pathway. - Source: PubMed
Publication date: 2026/03/18
Yang MinZhang XinyuDing YuXie LewenGao YuYao KangyuRen WanpingYang LiangZhao YankunShao Wei - Ribosome collisions act as molecular sensors of cellular stress, yet their role in disease physiology remains unclear. Here, we demonstrate that inhibition of the oncogenic kinase BCR::ABL1 in chronic myeloid leukemia (CML) cells induces ribosome collisions and activates the ribotoxic stress response (RSR). Clinical analyses revealed that CML progression from the chronic phase to the aggressive blast phase correlated with elevated expression of the RSR-initiating kinase ZAK. Although ZAK sustained CML cell proliferation by promoting AKT activity, loss of ZAK function paradoxically reduced the cytotoxic effects of BCR::ABL1 inhibitors. Mechanistically, BCR::ABL1 inhibition promoted phosphorylation of eukaryotic translation elongation factor 2 (EEF2) via the mTOR-EEF2K pathway, slowed translation elongation, and generated nuclease-resistant collided ribosomes that triggered ZAK-dependent p38 activation and apoptosis. Furthermore, pharmacological modulation of translation flux fine-tuned the efficacy of BCR::ABL1 inhibitors, including in primary patient cells. These findings define a ribosome-based stress pathway crucial for CML apoptosis and highlight ZAK-dependent RSR as a therapeutic vulnerability. - Source: PubMed
Publication date: 2026/03/30
Park JuminKim Soo-HyunPark JongminPark HeejuKim HongtaeKim Dong-WookLim Chunghun