Awan Aiman B, Osman Maryiam Jama Ali, Khan Omar M
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar.
Research Branch, Sidra Medicine, Doha P.O. Box 34110, Qatar.
Cells. 2025 Jan 7;14(2):69. doi: 10.3390/cells14020069.
Ubiquitination is cells' second most abundant posttranslational protein modification after phosphorylation. The ubiquitin-proteasome system (UPS) is critical in maintaining essential life processes such as cell cycle control, DNA damage repair, and apoptosis. Mutations in ubiquitination pathway genes are strongly linked to the development and spread of multiple cancers since several of the UPS family members possess oncogenic or tumor suppressor activities. This comprehensive review delves into understanding the ubiquitin code, shedding light on its role in cancer cell biology and immune evasion. Furthermore, we highlighted recent advances in the field for targeting the UPS pathway members for effective therapeutic intervention against human cancers. We also discussed the recent update on small-molecule inhibitors and PROTACs and their progress in preclinical and clinical trials.
泛素化是细胞中仅次于磷酸化的第二丰富的翻译后蛋白质修饰。泛素-蛋白酶体系统（UPS）在维持细胞周期调控、DNA损伤修复和细胞凋亡等基本生命过程中至关重要。由于UPS家族的几个成员具有致癌或肿瘤抑制活性，泛素化途径基因的突变与多种癌症的发生和扩散密切相关。这篇综述深入探讨了泛素密码，揭示了其在癌细胞生物学和免疫逃逸中的作用。此外，我们强调了该领域在靶向UPS途径成员以有效治疗人类癌症方面的最新进展。我们还讨论了小分子抑制剂和PROTAC的最新进展及其在临床前和临床试验中的进展。
