泛素-蛋白酶体系统（UPS）是细胞中一种基本的调控机制，对于维持细胞稳态、编排信号传导和决定细胞命运至关重要。这些生物过程需要UPS成员（包括泛素连接酶、泛素连接酶、去泛素化酶和蛋白酶体等）之间的协调信号级联，对底物进行泛素化和去泛素化。最近的研究表明，在胰腺癌中，泛素化编码的改写尤为突出。UPS成员的高频突变或异常高表达导致铁死症、肿瘤微环境和代谢重整过程紊乱，并促进肿瘤的生长、转移、免疫逃逸和获得性耐药性。我们对胰腺癌中的泛素化过程进行了深入的概述，突出了泛素编码在促进肿瘤和抑制肿瘤途径中的作用。此外，我们还回顾了当前的UPS调节剂，并分析了UPS调节剂作为癌症治疗的潜力。版权所有 © 2023。Elsevier B.V.出版。

The ubiquitin-proteasome system (UPS) is a fundamental regulatory mechanism in cells, vital for maintaining cellular homeostasis, compiling signaling transduction, and determining cell fates. These biological processes require the coordinated signal cascades of UPS members, including ubiquitin ligases, ubiquitin-conjugating enzymes, deubiquitinases, and proteasomes, to ubiquitination and de-ubiquitination on substrates. Recent studies indicate that ubiquitination code rewriting is particularly prominent in pancreatic cancer. High frequency mutation or aberrant hyperexpression of UPS members dysregulates ferroptosis, tumor microenvironment, and metabolic rewiring processes and contribute to tumor growth, metastasis, immune evasion, and acquired drug resistance. We conduct an in-depth overview of ubiquitination process in pancreatic cancer, highlighting the role of ubiquitin code in tumor-promoting and tumor-suppressor pathways. Furthermore, we review current UPS modulators and analyze the potential of UPS modulators as cancer therapy.Copyright © 2023. Published by Elsevier B.V.