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The Eukaryotic elongation factor 2 kinase (EEF2K) mRNA 3'-untranslated region (3'-UTR) is a critical regulatory segment of the EEF2K transcript that controls the expression of the EEF2K protein. EEF2K is a unique calcium/calmodulin-dependent alpha-kinase that phosphorylates and inactivates eukaryotic elongation factor 2 (eEF2), thereby inhibiting the elongation phase of protein synthesis (PubMed: 23791177). The 3'-UTR contains multiple binding sites for microRNAs, such as miR-603 and miR-200c, and RNA-binding proteins that modulate mRNA stability and translation (PubMed: 26433224). In many cancers, including glioblastoma and breast cancer, EEF2K is upregulated to promote cell survival under nutrient-deprived or hypoxic conditions by slowing down protein synthesis to conserve energy (PubMed: 21113130). Targeting the EEF2K mRNA 3'-UTR using antisense oligonucleotides or microRNA mimics represents a therapeutic strategy to suppress EEF2K expression, thereby sensitizing tumor cells to metabolic stress and chemotherapy. This approach aims to bypass the challenges of developing highly selective small-molecule inhibitors for the EEF2K protein itself by directly reducing the pool of available mRNA for translation (PubMed: 27197151).
Modulation of mRNA stability and translation efficiency through the binding of complementary microRNAs or antisense oligonucleotides to the 3'-untranslated region, leading to the degradation of the transcript or inhibition of protein synthesis of the eukaryotic elongation factor 2 kinase.
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