SUMO1, short for Small Ubiquitin-related Modifier 1, is involved in a dynamic post-translational modification process known as SUMOylation. This modification impacts multiple cellular functions, such as maintaining cardiac function, regulating protein solubility and aggregation, and influencing protein-protein interactions. SUMOylation is associated with pathways related to cell survival, stress response, and proteostasis [3]. Genetic models, like knockout (KO) mice, are valuable tools for studying SUMO1's functions.

In the context of myocardial infarction (MI), SUMO1 knockout in mice significantly exacerbated systolic dysfunction and infarct size. Single-nucleus RNA sequencing revealed its differential role in regulating heart cells. For example, in cardiomyocytes, SUMO1 deletion increased the proportion of a specific sub-cluster, while in fibroblasts, it inhibited their conversion to myofibroblasts. In endothelial cells, SUMO1 loss promoted the proliferation of subsets involved in neovascularization [1]. Systemic administration of a small-molecule degrader of SUMO1, HB007, inhibited the progression of patient-derived brain, breast, colon, and lung cancers in mice, increasing their survival. This indicates that SUMO1 may play a role in cancer progression [2]. In progressive supranuclear palsy (PSP), SUMO1 co-localizes with intraneuronal tau inclusions, and its modification of truncated tau may promote aggregation, contributing to PSP pathogenesis [4].

In conclusion, SUMO1 plays essential roles in multiple biological processes. Studies using KO mouse models have revealed its significance in diseases such as MI, cancer, and neurodegenerative disorders like PSP. Understanding SUMO1's functions provides insights into disease mechanisms and may help identify novel therapeutic targets for these conditions.