Psat1-KO Mouse

Psat1, or phosphoserine aminotransferase 1, is an enzyme in the serine biosynthesis pathway (SBP) [1,2,3,4,6,7,8,9]. SBP is a branch of glycolysis, and Psat1 is crucial for the production of metabolites like α-ketoglutarate (α-KG) and glutamine [1,7]. These metabolites play roles in bioenergetics, biomass generation, and as cofactors for chromatin modifiers, thus having broad impacts on cell biology [1].

Gene inactivation studies, such as in muscle stem cells (MuSCs), have shown that Psat1 ablation leads to defective expansion of MuSCs and impaired muscle regeneration [1]. This indicates that Psat1-generated α-KG and glutamine are essential for MuSC activation and myogenic progenitor expansion [1]. In old mice, reduced levels of Psat1, α-KG, and glutamine in MuSCs result in impaired muscle regeneration, which can be restored by α-KG or glutamine supplementation [1].

In cancer research, targeting PSAT1 shows promise. For example, in tumors with the p53-72Pro variant, depleting PSAT1 restores the interaction between p5372P and PGC-1α, suppressing metastasis [2]. In triple-negative breast cancer, miR-195-5p/PSAT1 regulatory axis exists, and upregulating miR-195-5p inhibits tumor behavior [3]. In estrogen receptor-negative breast cancer, PSAT1 promotes metastasis via the p-AKT/SP1/ITGA2 axis [4]. In clear cell renal cell carcinoma, PSAT1 enhances the efficacy of the prognosis estimation nomogram model [5]. In colorectal cancer, siRNA-mediated knockdown of PSAT1 promotes cell migration, invasion, proliferation, colony formation, and the EMT process, with PSAT1 affecting EMT by regulating the PI3K/AKT signaling pathway [6]. In breast cancer cells, PSAT1's unique catalytic property enables metabolic adaptation to glutamine blockade [7]. In high-glucose-induced retinal pigment epithelial cell injury, upregulating PSAT1 can attenuate cell apoptosis and oxidative stress [8]. In hepatoblastoma, LATS2 affects ferroptosis through the YAP1/ATF4/PSAT1 axis [9].

In summary, Psat1 is essential in multiple biological processes, especially in muscle stem cell activation and regeneration. Its role in various diseases, particularly cancer, has been highlighted through gene-inactivation models. These studies on Psat1 provide insights into its biological functions and potential therapeutic strategies for related diseases.

References:

1. Ciuffoli, Veronica, Feng, Xuesong, Jiang, Kan, Dell'Orso, Stefania, Sartorelli, Vittorio. 2024. Psat1-generated α-ketoglutarate and glutamine promote muscle stem cell activation and regeneration. In Genes & development, 38, 151-167. doi:10.1101/gad.351428.123. https://pubmed.ncbi.nlm.nih.gov/38453480/

2. Jiang, Jingwen, Chen, Hai-Ning, Jin, Ping, Yu, Qiang, Huang, Canhua. 2023. Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant. In Signal transduction and targeted therapy, 8, 65. doi:10.1038/s41392-022-01266-7. https://pubmed.ncbi.nlm.nih.gov/36788227/

3. Wang, Huiling, Fang, Qian, You, Shuo, Wu, Yaqin, Zhang, Chaojie. 2022. miRNA-195-5p/PSAT1 feedback loop in human triple-negative breast cancer cells. In Genes & genomics, 45, 39-47. doi:10.1007/s13258-022-01327-9. https://pubmed.ncbi.nlm.nih.gov/36371491/

4. Zhang, Xingda, Wang, Siyu, Li, Wei, Pang, Da, Gao, Song. 2024. PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell. In Biomolecules, 14, . doi:10.3390/biom14080990. https://pubmed.ncbi.nlm.nih.gov/39199378/

5. Wang, Jun, He, Xiaoming, Mi, Yuanyuan, Li, Jie, Wang, Rong. 2024. PSAT1 enhances the efficacy of the prognosis estimation nomogram model in stage-based clear cell renal cell carcinoma. In BMC cancer, 24, 463. doi:10.1186/s12885-024-12183-z. https://pubmed.ncbi.nlm.nih.gov/38614981/

6. Wang, Mingjin, Zhang, Houshun, Lu, Zhiyuan, Wang, Jiayu, Jia, Xiaoyi. 2024. PSAT1 mediated EMT of colorectal cancer cells by regulating Pl3K/AKT signaling pathway. In Journal of Cancer, 15, 3183-3198. doi:10.7150/jca.93789. https://pubmed.ncbi.nlm.nih.gov/38706897/

7. Qiu, Yijian, Stamatatos, Olivia T, Hu, Qingting, Cross, Justin R, Lukey, Michael J. 2024. The unique catalytic properties of PSAT1 mediate metabolic adaptation to glutamine blockade. In Nature metabolism, 6, 1529-1548. doi:10.1038/s42255-024-01104-w. https://pubmed.ncbi.nlm.nih.gov/39192144/

8. Du, Xiaofeng, Wang, Yanting, Gao, Fan. 2024. PSAT1 is upregulated by METTL3 to attenuate high glucose-induced retinal pigment epithelial cell apoptosis and oxidative stress. In Diagnostic pathology, 19, 138. doi:10.1186/s13000-024-01556-4. https://pubmed.ncbi.nlm.nih.gov/39407268/

9. Zhu, Guoqing, Xie, Yi, Bian, Zhixuan, Ding, Miao, Pan, Qiuhui. 2024. N6-methyladenosine modification of LATS2 promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis. In International journal of biological sciences, 20, 4146-4161. doi:10.7150/ijbs.92413. https://pubmed.ncbi.nlm.nih.gov/39247829/