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Last update 23 Jan 2025

EEF2K

Last update 23 Jan 2025

Basic Info

Synonyms

Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase, CaMKIII, eEF-2 kinase

+ [3]

Introduction

Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced.

Drugs associated with EEF2K

A-484954

Target

EEF2K

Mechanism

EEF2K inhibitors

Active Org.

Abbott Laboratories

Originator Org.

Abbott Laboratories

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

EEF2K inhibitors(Central South University)

Target

EEF2K

Mechanism

EEF2K inhibitors

Active Org.

Central South University

Originator Org.

Central South University

Active Indication

Triple Negative Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

eEF2K (Johns Hopkins University)

Target

EEF2K

Mechanism

EEF2K inhibitors

Active Org.-

Originator Org.

University of Medicine & Dentistry of New Jersey

Active Indication-

Inactive Indication

Alzheimer Disease [+3]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with EEF2K

100 Translational Medicine associated with EEF2K

0 Patents (Medical) associated with EEF2K

432

Literatures (Medical) associated with EEF2K

01 Dec 2025·Molecular Biology Reports

Comparing the malignant properties of parental and a knock-in version of HCT116 cell line expressing the CDK2-mutant of eukaryotic elongation factor 2 (eEF2)

Article

Author: Yüksel, B ; Deniz, A Aslı Hızlı ; Şahin, F ; Türkel, N

BACKGROUNDModulation of protein synthesis according to the physiological cues is maintained through tight control of Eukaryotic Elongation Factor 2 (eEF2), whose unique translocase activity is essential for cell viability. Phosphorylation of eEF2 at its Thr56 residue inactivates this function in translation. In our previous study we reported a novel mode of post-translational modification that promotes higher efficiency in T56 phosphorylation. Cyclin A/CDK2-mediated phosphorylation of eEF2 at the S595 residue is required for more potent phosphorylation at the Thr56, suggesting CDK2 takes a role in robust suppression of protein synthesis.METHODS AND RESULTSIn the current study, we analyzed the cell cycle, proliferation, cell death, migration, colony formation, autophagy, and response to Cisplatin properties of the point-mutant variant of HCT116 cells that express the CDK2 mutant (S595A-eEF2) of eEF2. The knocked in S595A mutation resulted in decreased levels of T56 phosphorylation of eEF2, which appears to have similar biological consequences to other experimental manipulations such as silencing the activity of the kinase for the Thr56 residue, eEF2 Kinase (eEF2K).CONCLUSIONOur findings indicate that interfering with the inhibition of eEF2 results in elevated protein synthesis in HCT116 cells and is associated with the progression of malignancy in the colorectal cancer cell line, where eEF2K activity could provide a tumor suppressive role.

01 Jan 2025·Journal of Neurochemistry

Indole and Coumarin Derivatives Targeting EEF2K in Aβ Folding Reporter Cells

Article

Author: Lin, Chih‐Hsin ; Lin, Te‐Hsien ; Chi, Shun‐Tzu ; Yao, Ching‐Fa ; Lin, Wenwei ; Chen, Chiung‐Mei ; Wei, Pei‐Cih ; Chiu, Ya‐Jen ; Lee‐Chen, Guey‐Jen ; Chang, Kuo‐Hsuan

ABSTRACTMisfolding and accumulation of amyloid‐β (Aβ) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on Aβ folding and EEF2 signaling using SH‐SY5Y cells expressing Aβ‐green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009‐1, ‐6) and two coumarin (LM‐021, ‐036) derivatives effectively reduced Aβ misfolding and associated reactive oxygen species (ROS) production. Additionally, these compounds decreased acetylcholinesterase and caspase‐3/‐6 activities while promoting neurite outgrowth. NC009‐1 increased active phosphorylation of extracellular‐signal regulated kinase (ERK) (T202/Y204), leading to an increase in inactive eukaryotic elongation factor 2 kinase (EEF2K) phosphorylation (S366). LM‐021 decreased the active phosphorylation of AMP‐activated protein kinase (AMPK) (T172) and EEF2K (S398), while LM‐036 exhibited dual effects, increasing inactive phosphorylation and decreasing active phosphorylation of EEF2K. These changes in EEF2K phosphorylation led to decreased EEF2K activity and a subsequent reduction in inactive phosphorylation of EEF2 (T56). This cascade further promoted the phosphorylation of transcription factor cAMP‐response‐element binding protein (CREB) (S133) and the expression of brain‐derived neurotrophic factor (BDNF), and reduced BCL‐2 associated X‐protein (BAX)/B‐cell lymphoma 2 (BCL2) ratio. Knockdown of EEF2 abolished the effects of NC009‐1, LM‐021, and LM‐036 on CREB phosphorylation, BDNF expression, caspase‐3 activity, and neurite outgrowth. These findings demonstrate that NC009‐1, LM‐021, and LM‐036 exert their neuroprotective effects through modulation of EEF2K signaling, highlighting their potentials as therapeutic candidates for AD.

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01 Jan 2025·British Journal of Pharmacology

Pharmacokinetics and cardioprotective efficacy of intravenous miR‐125b* microRNA mimic in a mouse model of acute myocardial infarction

Article

Author: Gömöri, Kamilla ; Vörös, Imre ; Szabados, Tamara ; Váradi, Barnabás ; Ágg, Bence ; Benczik, Bettina ; Bencsik, Péter ; Ferdinandy, Péter ; Makkos, András ; Varga, Zoltán V. ; Brenner, Gábor G. ; Görbe, Anikó ; Szabó, Márta

AbstractBackground and purposeMicroRNA (miRNA) therapy is a promising approach to induce cardioprotection. We have previously identified cardiac microRNA‐125b* (microRNA‐125b‐2‐3p; miR‐125b*) as a potential cardioprotective miRNA, termed ProtectomiR. We aimed to characterize the pharmacokinetics and pharmacodynamics, and the effect of miR‐125b* mimic on infarct size using an in vivo mouse model.Experimental approachTo characterize the pharmacokinetics properties of miR‐125b* mimic, a single injection of 10‐μg miR‐125b* mimic or its scramble miRNA control, or vehicle i.v. was given to C57BL/6 mice. MiR‐125b* expression was measured from plasma, heart, kidney and liver samples. Effect of miR‐125b* on area at risk and infarct size was assessed after 45‐min coronary occlusion, followed by 24‐h reperfusion; 10‐μg miR‐125b* mimic or 10‐μg non‐targeting miRNA mimic control or vehicle were administered via the right jugular vein at 10th mins of coronary occlusion. To assess molecular mechanism involved in cardioprotection, expression of mRNA targets of miR‐125b* were measured from ventricular myocardium at 1, 2, 4, 8 or 24 h post‐treatment using quantitative real time polymerase chain reaction.Key resultsMiR‐125b* expression was markedly increased in plasma and myocardium 1 h, and in the liver 2h after treatment. Infarct size was significantly reduced after miR‐125b* mimic treatment when compared to the vehicle. The expression of Ccna2, Eef2k and Cacnb2 target mRNAs was significantly reduced 8 h after injection of miR‐125b* mimic.Conclusion and implicationsThis is the first demonstration of pharmacokinetic and molecular pharmacodynamic properties as well as the cardioprotective effect of miR‐125b* mimic in vivo.LINKED ARTICLESThis article is part of a themed issue Non‐coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc

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EEF2K

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