EEF1D, also known as eukaryotic translation elongation factor 1 delta, is part of the EEF1 protein complex. It can produce four protein isoforms, with three short isoforms acting as translation elongation factors, involved in anti-aging, cell cycle regulation, and the development of malignant tumors. The long-form isoform is crucial for nervous system development. EEF1D is involved in various biological processes, and its study in genetic models like KO mouse models can help uncover its functions [1,4,5].

EEF1D knockdown in primary bovine mammary epithelial cells led to abnormal cytoplasmic lipid droplet formation and a significant decrease in milk triglyceride levels, indicating its role in milk lipid synthesis via insulin (PI3K-Akt), AMPK, and PPAR pathways. In EEF1D CRISPR/Cas9 knockout mice, incompletely developed mammary glands and decreased milk triglyceride concentration were observed, along with gene expression alterations in the three pathways [2]. In glioma, knockdown of EEF1D reduced cell proliferation and impaired epithelial-mesenchymal transition (EMT) phenotypes, suggesting its role in promoting glioma cell proliferation, migration, and invasion through PI3K/Akt and EMT pathways [3]. In ovarian cancer, interfering with EEF1D gene expression enhanced the sensitivity of cancer cells to cisplatin, potentially by inactivating the PI3K/AKT signaling pathway [6].

In summary, EEF1D plays essential roles in multiple biological processes. Its functions in milk lipid synthesis, as well as in the development and treatment-related aspects of various cancers and neurodevelopmental disorders, have been revealed through model-based research, especially KO mouse models. These findings contribute to understanding disease mechanisms and developing potential therapeutic strategies for related diseases [1,2,3,5,6].

References:

1. Xu, Hui, Yu, Shaobin, Peng, Kaiming, Chen, Shuchen, Kang, Mingqiang. . The role of EEF1D in disease pathogenesis: a narrative review. In Annals of translational medicine, 9, 1600. doi:10.21037/atm-21-5025. https://pubmed.ncbi.nlm.nih.gov/34790806/

2. Hou, Yali, Xie, Yan, Yang, Shaohua, Zhang, Qin, Sun, Dongxiao. . EEF1D facilitates milk lipid synthesis by regulation of PI3K-Akt signaling in mammals. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e21455. doi:10.1096/fj.202000682RR. https://pubmed.ncbi.nlm.nih.gov/33913197/

3. Xie, Cheng, Zhou, Mingfeng, Lin, Jie, Xue, Shuaishuai, Song, Ye. 2020. EEF1D Promotes Glioma Proliferation, Migration, and Invasion through EMT and PI3K/Akt Pathway. In BioMed research international, 2020, 7804706. doi:10.1155/2020/7804706. https://pubmed.ncbi.nlm.nih.gov/33029523/

4. Kaitsuka, Taku, Matsushita, Masayuki. 2015. Regulation of translation factor EEF1D gene function by alternative splicing. In International journal of molecular sciences, 16, 3970-9. doi:10.3390/ijms16023970. https://pubmed.ncbi.nlm.nih.gov/25686034/

5. Averdunk, Luisa, Al-Thihli, Khalid, Surowy, Harald, Al-Maawali, Almundher, Wieczorek, Dagmar. 2023. Expanding the spectrum of EEF1D neurodevelopmental disorders: Biallelic variants in the guanine exchange domain. In Clinical genetics, 103, 484-491. doi:10.1111/cge.14290. https://pubmed.ncbi.nlm.nih.gov/36576126/

6. Xu, Qia, Liu, Yun, Wang, Shenyi, Xu, Yin, Qin, Yide. 2022. Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin. In BMC cancer, 22, 628. doi:10.1186/s12885-022-09699-7. https://pubmed.ncbi.nlm.nih.gov/35672728/