Senp3-KO Mouse

Senp3, short for SUMO-specific protease 3, is a crucial enzyme in the regulation of protein SUMOylation. SUMOylation is a protein modification process, and Senp3's role in de-SUMOylation influences protein function, localization, stability, and interactions, thereby regulating diverse cellular processes. It is involved in multiple signaling pathways and has significance in maintaining genome stability, cell growth, and division [4].

In cancer research, DC-specific deletion of Senp3 in mice blunts STING-dependent type-I interferon signaling in dendritic cells, dampening antitumor immune responses, indicating its importance in STING-mediated DC antitumor immune responses [1]. Macrophage-specific deletion of Senp3 promotes M2 macrophage polarization and breast cancer progression, as it enhances Akt1 SUMOylation, leading to Akt1 hyper-phosphorylation and activation [2]. In hepatocellular carcinoma, METTL16-mediated regulation of Senp3 mRNA stability affects ferroptosis resistance and tumorigenesis [3]. Also, in prostate cancer, Senp3 is highly expressed and promotes cancer cell proliferation and migration by mediating deSUMOylation of SIX1 [5]. In non-cancer diseases, myeloid-specific Senp3 knockout inhibits abdominal aortic aneurysm (AAA) formation in mouse models, as Senp3-mediated CTH deSUMOylation regulates macrophage ferroptosis and AAA development [6].

In summary, Senp3 plays essential roles in various biological processes, especially in the context of cancer and certain inflammatory disorders. Gene knockout and conditional knockout mouse models have been instrumental in revealing Senp3's functions in antitumor immune responses, cancer progression, and the development of aortic aneurysmal diseases. These findings provide potential therapeutic targets and a better understanding of the underlying molecular mechanisms in these disease areas.

References:

1. Hu, Zhilin, Teng, Xiao-Lu, Zhang, Tianyu, Wang, Zhengting, Zou, Qiang. . SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function. In Molecular cell, 81, 940-952.e5. doi:10.1016/j.molcel.2020.12.024. https://pubmed.ncbi.nlm.nih.gov/33434504/

2. Xiao, Ming, Bian, Qi, Lao, Yimin, Sun, Xuxu, Yang, Jie. 2021. SENP3 loss promotes M2 macrophage polarization and breast cancer progression. In Molecular oncology, 16, 1026-1044. doi:10.1002/1878-0261.12967. https://pubmed.ncbi.nlm.nih.gov/33932085/

3. Wang, Jialin, Xiu, Mengxi, Wang, Jin, Gao, Yong, Li, Yandong. 2024. METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma. In Journal of hematology & oncology, 17, 78. doi:10.1186/s13045-024-01599-6. https://pubmed.ncbi.nlm.nih.gov/39218945/

4. Chen, Lianglong, Che, Yaning, Huang, Chao. 2025. SENP3: Cancers and diseases. In Biochimica et biophysica acta. Reviews on cancer, 1880, 189260. doi:10.1016/j.bbcan.2025.189260. https://pubmed.ncbi.nlm.nih.gov/39765284/

5. Shao, Zhenlong, Liu, Shutong, Sun, Wenshuang, Liu, Jinbao, Huang, Hongbiao. 2024. SENP3 mediates deSUMOylation of SIX1 to promote prostate cancer proliferation and migration. In Cellular & molecular biology letters, 29, 146. doi:10.1186/s11658-024-00665-8. https://pubmed.ncbi.nlm.nih.gov/39623295/

6. Chen, Long, Cai, Zhaohua, Xiao, Danrui, Shao, Qin, He, Ben. 2025. SENP3 Drives Abdominal Aortic Aneurysm Development by Regulating Ferroptosis via De-SUMOylation of CTH. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2414500. doi:10.1002/advs.202414500. https://pubmed.ncbi.nlm.nih.gov/40019399/