Gspt2-KO Mouse

Gspt2, also known as eukaryotic peptide chain release factor GTP-binding subunit eRF3b, is involved in the termination of protein synthesis in eukaryotes. It is one of the two mammalian genes encoding eRF3 structural homologues, with the other being Gspt1. It may interact with eRF1 to function as eRF3 in mammalian cells, and its mRNA is differentially expressed in various tissues, with relatively abundant levels in the brain [1,4].

Mouse studies have shown that Gspt2, but not Gspt1, can functionally substitute the essential yeast gene SUP35, indicating functional differences between the two proteins [1]. In humans, deletions of Xp11.22 region encompassing Gspt2 are associated with syndromic X-linked intellectual disability, suggesting that loss-of-function of Gspt2 may contribute to intellectual disability and developmental delay [2,5]. Also, Gspt2 has been identified as a biomarker for hepatocellular carcinoma, promoting HepG2 cells' entrance into the S-phase and influencing the phosphorylation status of 4E-BP1 [3].

In conclusion, Gspt2 plays a crucial role in protein translation termination and has implications in human diseases such as X-linked intellectual disability and hepatocellular carcinoma. Studies, including those using mouse models substituting yeast genes, have provided insights into its unique functions, highlighting its significance in understanding biological processes and disease mechanisms.

References:

1. Le Goff, Catherine, Zemlyanko, Olga, Moskalenko, Svetlana, Philippe, Michel, Zhouravleva, Galina. . Mouse GSPT2, but not GSPT1, can substitute for yeast eRF3 in vivo. In Genes to cells : devoted to molecular & cellular mechanisms, 7, 1043-57. doi:. https://pubmed.ncbi.nlm.nih.gov/12354098/

2. Grau, Christina, Starkovich, Molly, Azamian, Mahshid S, Lalani, Seema R, Scott, Daryl A. 2017. Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability. In PloS one, 12, e0175962. doi:10.1371/journal.pone.0175962. https://pubmed.ncbi.nlm.nih.gov/28414775/

3. Li, Man, Wang, Jian, Yang, Lei, Tian, Qing-Bao, Liu, Dian-Wu. 2014. eRF3b, a biomarker for hepatocellular carcinoma, influences cell cycle and phosphoralation status of 4E-BP1. In PloS one, 9, e86371. doi:10.1371/journal.pone.0086371. https://pubmed.ncbi.nlm.nih.gov/24466059/

4. Hoshino, S, Imai, M, Mizutani, M, Ui, M, Katada, T. . Molecular cloning of a novel member of the eukaryotic polypeptide chain-releasing factors (eRF). Its identification as eRF3 interacting with eRF1. In The Journal of biological chemistry, 273, 22254-9. doi:. https://pubmed.ncbi.nlm.nih.gov/9712840/

5. Al-Shehhi, Halima, Gabr, Ahlam, Al-Haddabi, Intisar, Al-Maamari, Watfa, Al-Maawali, Almundher. . Further Clinical and Molecular Delineation of Xp11.22 Deletion Syndrome: A Case Report. In Oman medical journal, 34, 460-463. doi:10.5001/omj.2019.83. https://pubmed.ncbi.nlm.nih.gov/31555424/