Eef1akmt3-KO Mouse

Eef1akmt3, also known as METTL21B, is a lysine methyltransferase. It specifically targets and methylates eukaryotic translation elongation factor 1 alpha (eEF1A) at Lys-165, affecting mRNA translation [3,4,5]. It is involved in multiple biological processes, and its dysregulation is associated with diseases such as cancer [1,3]. Gene knockout models can be valuable for studying its functions in vivo.

In gastric cancer, Eef1akmt3 expression was lower in cancer tissues, and its knockdown increased tumor invasiveness and migration. Eef1akmt3 was identified as a tumor-suppressive methyltransferase that catalyzes the monomethylation of MAP2K7 at K296, reducing the phosphorylation, ubiquitination, and degradation of TP53. This reveals the tumor-suppressive function of the Eef1akmt3/MAP2K7/TP53 signaling axis, suggesting it as a potential targeted therapy for gastric cancer [1]. In endothelial cells, RIPK1 phosphorylates Eef1akmt3 at Ser26, inhibiting its methyltransferase activity and global protein synthesis, which attenuates N-Shh translation and secretion. Endothelial RIPK1 knockout exacerbated graft stenosis, and treatment with a Hedgehog pathway inhibitor alleviated this, indicating a protective role of endothelial RIPK1-regulated Eef1akmt3 in arterial bypass graft vascular remodeling [2].

In conclusion, Eef1akmt3 is a significant methyltransferase involved in mRNA translation and protein methylation. Through gene-knockout-based research, its role in suppressing tumor invasiveness and metastasis in gastric cancer and in protecting artery bypass grafts from arteriosclerosis has been revealed. These findings contribute to understanding the underlying mechanisms of related diseases and may provide new therapeutic strategies.

References:

1. Hong, Yo Han, Aziz, Nur, Park, Jae Gwang, Hur, Hoon, Cho, Jae Youl. 2022. The EEF1AKMT3/MAP2K7/TP53 axis suppresses tumor invasiveness and metastasis in gastric cancer. In Cancer letters, 544, 215803. doi:10.1016/j.canlet.2022.215803. https://pubmed.ncbi.nlm.nih.gov/35753528/

2. Lu, Yao, Leng, Yiming, Li, Yalan, Weng, Liang, Xu, Qingbo. 2023. Endothelial RIPK1 protects artery bypass graft against arteriosclerosis by regulating SMC growth. In Science advances, 9, eadh8939. doi:10.1126/sciadv.adh8939. https://pubmed.ncbi.nlm.nih.gov/37647392/

3. Shu, Xin, Li, Xinquan, Xiang, Xiaochen, Wang, Qiang, Wu, Qingming. 2021. METTL21B is a prognostic biomarker and potential therapeutic target in low-grade gliomas. In Aging, 13, 20661-20683. doi:10.18632/aging.203454. https://pubmed.ncbi.nlm.nih.gov/34446611/

4. Hamey, Joshua J, Wienert, Beeke, Quinlan, Kate G R, Wilkins, Marc R. 2017. METTL21B Is a Novel Human Lysine Methyltransferase of Translation Elongation Factor 1A: Discovery by CRISPR/Cas9 Knockout. In Molecular & cellular proteomics : MCP, 16, 2229-2242. doi:10.1074/mcp.M116.066308. https://pubmed.ncbi.nlm.nih.gov/28663172/

5. Malecki, Jedrzej, Aileni, Vinay Kumar, Ho, Angela Y Y, Leidel, Sebastian A, Falnes, Pål Ø. . The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A). In Nucleic acids research, 45, 4370-4389. doi:10.1093/nar/gkx002. https://pubmed.ncbi.nlm.nih.gov/28108655/