G3bp1-KO Mouse

G3bp1, also known as Ras-GTPase-activating protein binding protein 1, is a multifunctional binding protein involved in numerous biological functions. It plays a key role in cell proliferation, metastasis, apoptosis, differentiation, and RNA metabolism. It is central to the formation of stress granules (SGs) through liquid-liquid phase separation (LLPS), triggered by an increase in intracellular free RNA concentrations [1]. G3bp1 also affects DNA sensing as it promotes DNA binding and activation of cGAS [3].

In the context of disease, G3bp1 has been shown to have varied roles. In cancers, it acts as a cancer-promoting factor, enhancing the proliferation, invasion, and metastasis of cancer cells. For example, in bladder cancer, it promotes immune evasion by downregulating MHC-I via PI3K/Akt activation [2,7]. In viral infections, it can act as an antiviral factor by interacting with viral proteins and regulating SG assembly to inhibit viral replication, yet some viruses hijack it to promote their own proliferation [2]. In neurodegenerative diseases related to impaired SG disassembly, ubiquitination of G3bp1 has been shown to mediate SG disassembly in a context-specific manner, and TRIM21-mediated ubiquitination of G3bp1 is involved in SG homeostasis [4,5]. Also, a G3bp1-interacting lncRNA can promote ferroptosis and apoptosis in cancer via nuclear sequestration of p53, and a G3bp1-FBXL5-IRP2 axis determines sodium arsenite-induced ferroptosis [6,8].

In conclusion, G3bp1 is a crucial protein involved in a wide range of biological functions and disease processes. Its role in stress granule formation, DNA sensing, and various disease conditions such as cancer, viral infections, and neurodegenerative diseases has been revealed through multiple studies. Understanding G3bp1 provides insights into the underlying mechanisms of these diseases and may offer potential therapeutic targets.

References:

1. Yang, Peiguo, Mathieu, Cécile, Kolaitis, Regina-Maria, Kim, Hong Joo, Taylor, J Paul. . G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules. In Cell, 181, 325-345.e28. doi:10.1016/j.cell.2020.03.046. https://pubmed.ncbi.nlm.nih.gov/32302571/

2. Ge, Yidong, Jin, Jiabei, Li, Jinyun, Ye, Meng, Jin, Xiaofeng. 2022. The roles of G3BP1 in human diseases (review). In Gene, 821, 146294. doi:10.1016/j.gene.2022.146294. https://pubmed.ncbi.nlm.nih.gov/35176431/

3. Liu, Zhao-Shan, Cai, Hong, Xue, Wen, Zhang, Xue-Min, Li, Tao. 2018. G3BP1 promotes DNA binding and activation of cGAS. In Nature immunology, 20, 18-28. doi:10.1038/s41590-018-0262-4. https://pubmed.ncbi.nlm.nih.gov/30510222/

4. Gwon, Youngdae, Maxwell, Brian A, Kolaitis, Regina-Maria, Kim, Hong Joo, Taylor, J Paul. 2021. Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner. In Science (New York, N.Y.), 372, eabf6548. doi:10.1126/science.abf6548. https://pubmed.ncbi.nlm.nih.gov/34739333/

5. Yang, Cuiwei, Wang, Zhangshun, Kang, Yingjin, Bai, Yun, Liu, Yanfen. 2023. Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3BP1 and autophagy-dependent elimination of stress granules. In Autophagy, 19, 1934-1951. doi:10.1080/15548627.2022.2164427. https://pubmed.ncbi.nlm.nih.gov/36692217/

6. Mao, Chao, Wang, Xiang, Liu, Yating, Yu, Herbert, Tao, Yongguang. 2018. A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53. In Cancer research, 78, 3484-3496. doi:10.1158/0008-5472.CAN-17-3454. https://pubmed.ncbi.nlm.nih.gov/29588351/

7. Zheng, Xianchong, Chen, Jiawei, Deng, Minhua, Kang, Tiebang, Liu, Zhuowei. 2023. G3BP1 and SLU7 Jointly Promote Immune Evasion by Downregulating MHC-I via PI3K/Akt Activation in Bladder Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2305922. doi:10.1002/advs.202305922. https://pubmed.ncbi.nlm.nih.gov/38084438/

8. Liu, Qian, Wang, Fengli, Chen, Yingxian, Cui, Hengkang, Wu, Hao. 2023. A regulatory module comprising G3BP1-FBXL5-IRP2 axis determines sodium arsenite-induced ferroptosis. In Journal of hazardous materials, 465, 133038. doi:10.1016/j.jhazmat.2023.133038. https://pubmed.ncbi.nlm.nih.gov/38118197/