Gspt1-KO Mouse

Gspt1, also known as G1 to S phase transition 1, is a key translation termination factor. It interacts with eRF1 to facilitate translation termination, playing a vital role in protein synthesis, a fundamental biological process [1,2].

Studies have shown that Gspt1 is significantly overexpressed in various cancer tissues and cells, including acute myeloid leukemia, MYC-driven lung cancer, liver cancer, and glioblastoma [1,2,4,5]. In acute myeloid leukemia, drugs that degrade Gspt1 via the CRL4CRBN ubiquitin ligase lead to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death, sparing normal hematopoietic stem cells [3]. In glioblastoma, depletion of Gspt1 using a cereblon modulator or knockout cells leads to enhanced apoptosis and longer survival in mice with transplanted tumors [5].

In conclusion, Gspt1 is essential for translation termination. Its overexpression in multiple cancers makes it a promising anti-tumor target. The use of Gspt1-degrading drugs and gene knockout models in in vivo studies has provided insights into its role in cancer, offering potential new strategies for cancer treatment [1,2,3,5].

References:

1. Zhang, Dandan, Lin, Pei, Lin, Jun. 2023. Molecular glues targeting GSPT1 in cancers: A potent therapy. In Bioorganic chemistry, 143, 107000. doi:10.1016/j.bioorg.2023.107000. https://pubmed.ncbi.nlm.nih.gov/38029571/

2. Chang, Xiujin, Qu, Fangui, Li, Chunxiao, Li, Zhiyu, Xu, Xi. 2024. Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective. In Medicinal research reviews, 44, 1727-1767. doi:10.1002/med.22024. https://pubmed.ncbi.nlm.nih.gov/38314926/

3. Sellar, Rob S, Sperling, Adam S, Słabicki, Mikołaj, Chen, Chun-Wei, Ebert, Benjamin L. . Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells. In The Journal of clinical investigation, 132, . doi:10.1172/JCI153514. https://pubmed.ncbi.nlm.nih.gov/35763353/

4. Xi, Yi-Qing, Gao, Jing-Bo, Li, Xuan-Fei, Feng, Mao-Hui, Zhang, Jing-Wei. 2022. GSPT1 Functions as a Tumor Promoter in Human Liver Cancer. In Current medical science, 43, 104-114. doi:10.1007/s11596-022-2665-6. https://pubmed.ncbi.nlm.nih.gov/36459303/

5. Sasayama, Takashi, Hamada, Takeshi, Tanaka, Kazuhiro, Yamanishi, Shunsuke, Ueyama, Takehiko. 2024. Potential of GSPT1 as a novel target for glioblastoma therapy. In Cell death & disease, 15, 572. doi:10.1038/s41419-024-06967-1. https://pubmed.ncbi.nlm.nih.gov/39117611/