Eif3d-KO Mouse

Eif3d, eukaryotic translation initiation factor 3d, is an RNA-binding subunit of the eIF3 complex. It has an RNA-binding motif and a cap-binding domain. Eif3d is involved in maintaining eIF3 complex integrity and global protein synthesis. It also plays a role in non-canonical cap-dependent translation of specific mRNAs, which is crucial for various biological and pathological processes [2].

During persistent stress, eIF3d activates the translation of the kinase GCN2, inducing eIF2α phosphorylation and inhibiting general protein synthesis. In parallel, it upregulates the m6A demethylase ALKBH5 to drive 5' UTR-specific demethylation of stress response genes like ATF4, ultimately controlling the integrated stress response (ISR) [1]. In cervical carcinoma, EIF3D promotes cell growth and the Warburg effect by interacting with GRP78 [3]. In colorectal cancer, EIF3D promotes resistance to 5-fluorouracil through upregulating RUVBL1 [4].

In conclusion, Eif3d is essential for regulating translation processes and has significant implications in stress responses and multiple diseases such as cervical carcinoma and colorectal cancer. Studies on Eif3d, especially through loss-of-function experiments, help in understanding its role in these biological processes and provide potential therapeutic targets for related diseases.

References:

1. Mukhopadhyay, Shaoni, Amodeo, Maria E, Lee, Amy S Y. 2023. eIF3d controls the persistent integrated stress response. In Molecular cell, 83, 3303-3313.e6. doi:10.1016/j.molcel.2023.08.008. https://pubmed.ncbi.nlm.nih.gov/37683648/

2. Ma, Shijie, Liu, Jing-Yuan, Zhang, Jian-Ting. 2023. eIF3d: A driver of noncanonical cap-dependent translation of specific mRNAs and a trigger of biological/pathological processes. In The Journal of biological chemistry, 299, 104658. doi:10.1016/j.jbc.2023.104658. https://pubmed.ncbi.nlm.nih.gov/36997088/

3. Liu, Qing, Liu, Jing, Zheng, Dan, Zhou, Xiaochan, Qin, Juan. 2022. EIF3D promoted cervical carcinoma through Warburg effect by interacting with GRP78. In Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology, 43, 2130200. doi:10.1080/01443615.2022.2130200. https://pubmed.ncbi.nlm.nih.gov/36264610/

4. Li, Chaobin, Lu, Kemei, Yang, Chenggang, Du, Wenfeng, Liang, Zhengkai. 2023. EIF3D promotes resistance to 5-fluorouracil in colorectal cancer through upregulating RUVBL1. In Journal of clinical laboratory analysis, 37, e24825. doi:10.1002/jcla.24825. https://pubmed.ncbi.nlm.nih.gov/36592991/