Furin-KO Mouse

Furin, the best-characterized member of the mammalian proprotein convertases, is a ubiquitously expressed single-pass type 1 transmembrane protein [1]. It catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway, regulating the maturation of numerous proproteins involved in various physiological and pathophysiological processes from embryonic development to carcinogenesis [1,2].

Furin knockout is embryonically lethal, while its knockout in differentiated somatic cells is not [1]. In SARS-CoV-2 infection, cleavage of the spike protein by furin promotes viral entry into lung cells, suggesting furin as a potential therapeutic target for viral pathogens [1,5,6]. In cancer, furin expression and activity are involved in carcinogenesis, but its inhibition may have different effects in different types of cancer [2]. In cystic fibrosis airways disease, elevated furin levels contribute to disease pathogenesis by activating key processes [3]. Emerging evidence also implicates furin in neurodegenerative and neuropsychiatric diseases, though its role in neurological diseases is less understood compared to cancer and infectious diseases [4].

In conclusion, furin is essential for the proteolytic maturation of many proproteins, playing a significant role in multiple biological processes and diseases. The study of furin knockout in differentiated somatic cells has revealed its potential as a therapeutic target in areas such as viral infections, cancer, and cystic fibrosis, providing valuable insights for developing treatment strategies [1,2,3].

References:

1. Osman, Essam Eldin A, Rehemtulla, Alnawaz, Neamati, Nouri. 2021. Why All the Fury over Furin? In Journal of medicinal chemistry, 65, 2747-2784. doi:10.1021/acs.jmedchem.1c00518. https://pubmed.ncbi.nlm.nih.gov/34340303/

2. He, Zongsheng, Khatib, Abdel-Majid, Creemers, John W M. 2022. The proprotein convertase furin in cancer: more than an oncogene. In Oncogene, 41, 1252-1262. doi:10.1038/s41388-021-02175-9. https://pubmed.ncbi.nlm.nih.gov/34997216/

3. Douglas, Lisa E J, Reihill, James A, Montgomery, Bethany M, Martin, S Lorraine. 2023. Furin as a therapeutic target in cystic fibrosis airways disease. In European respiratory review : an official journal of the European Respiratory Society, 32, . doi:10.1183/16000617.0256-2022. https://pubmed.ncbi.nlm.nih.gov/37137509/

4. Zhang, Yi, Gao, Xiaoqin, Bai, Xue, Chang, Yan-Zhong, Gao, Guofen. 2022. The emerging role of furin in neurodegenerative and neuropsychiatric diseases. In Translational neurodegeneration, 11, 39. doi:10.1186/s40035-022-00313-1. https://pubmed.ncbi.nlm.nih.gov/35996194/

5. Jiang, Xia, Li, Dabing, Maghsoudloo, Mazaher, Ma, Wenzhe, Fu, Junjiang. 2024. Targeting furin, a cellular proprotein convertase, for COVID-19 prevention and therapeutics. In Drug discovery today, 29, 104026. doi:10.1016/j.drudis.2024.104026. https://pubmed.ncbi.nlm.nih.gov/38762086/

6. Thomas, Gary, Couture, Frédéric, Kwiatkowska, Anna. 2022. The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2. In International journal of molecular sciences, 23, . doi:10.3390/ijms23073435. https://pubmed.ncbi.nlm.nih.gov/35408793/