SAE1, the SUMO-activating enzyme subunit 1, is a key component of the heterodimeric small ubiquitin-related modifier that is indispensable for protein SUMOylation. SUMOylation is a post-translational modification involved in multiple cellular events such as transcription regulation, cell cycle, and apoptosis [2,3,5,6]. Dysregulation of SAE1 has been associated with the progression of several diseases, making it an important target for research. Genetic models, like KO or CKO mouse models, could potentially be used to further explore its functions.

In multiple cancers, SAE1 has been shown to play a promoting role. In intrahepatic cholangiocarcinoma, Circ-RAPGEF5 promotes tumor progression by stabilizing SAE1 to facilitate SUMOylation, suggesting targeting SAE1 could be a novel strategy [1]. In glioma, SAE1 promotes cancer progression via enhancing AKT SUMOylation-mediated signaling pathway, and its silence inhibits glioma cell proliferation and tumor xenograft growth [2]. In gastric cancer, Helicobacter pylori infection upregulates SAE1 through ROS, and suppression of SAE1 attenuates epithelial-mesenchymal transition and cell proliferation abilities induced by H. pylori [3]. In breast cancer, SAE1 is highly expressed, associated with poor prognosis, and knockdown of SAE1 inhibits cell proliferation and the cell cycle process [4]. In hepatocellular carcinoma, SAE1 is over-expressed, has excellent diagnostic value, and its oncogenic effect is associated with dysregulated cancer metabolic signaling [5]. In addition, in rheumatoid arthritis, increased SAE1 in fibroblast-like synoviocytes promotes glycolysis and pathogenic behavior [7].

In conclusion, SAE1 is crucial in protein SUMOylation and is involved in the development of various diseases, especially cancers and rheumatoid arthritis. Studies using genetic models in these disease areas would be valuable, as current research mainly from cell and animal models shows that SAE1 promotes disease progression, suggesting it could be a potential therapeutic target.