Public Health Research Institute, Rutgers University, New Brunswick, NJ, United States.
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University, Newark, NJ, United States.
Front Cell Infect Microbiol. 2021 Nov 10;11:774613. doi: 10.3389/fcimb.2021.774613. eCollection 2021.
Ubiquitin-proteasome mediated protein turnover is an important regulatory mechanism of cellular function in eukaryotes. Extensive studies have linked the ubiquitin-proteasome system (UPS) to human diseases, and an array of proteasome inhibitors have been successfully developed for cancer therapy. Although still an emerging field, research on UPS regulation of fungal development and virulence has been rapidly advancing and has generated considerable excitement in its potential as a target for novel drugs. In this review, we summarize UPS composition and regulatory function in pathogenic fungi, especially in stress responses, host adaption, and fungal pathogenesis. Emphasis will be given to UPS regulation of pathogenic factors that are important for fungal pathogenesis. We also discuss future potential therapeutic strategies for fungal infections based on targeting UPS pathways.
泛素-蛋白酶体介导的蛋白质降解是真核细胞中细胞功能的重要调节机制。大量研究将泛素-蛋白酶体系统 (UPS) 与人类疾病联系起来,并且已经成功开发出多种蛋白酶体抑制剂用于癌症治疗。尽管 UPS 调节真菌发育和毒力的研究仍然是一个新兴领域,但它作为新型药物靶点的潜力正在迅速发展,并引起了相当大的关注。在这篇综述中,我们总结了 UPS 在病原真菌中的组成和调节功能,特别是在应激反应、宿主适应和真菌发病机制中的作用。重点将放在 UPS 对真菌发病机制中重要的致病因子的调节上。我们还讨论了基于靶向 UPS 途径的真菌感染的未来潜在治疗策略。