文献类型： 外文期刊
第一作者： Lv, Shengnan
作者： Lv, Shengnan;Zhang, Jian;Peng, Xinyu;Liu, Huan;Wei, Feng;Liu, Yan
作者机构：
关键词： pancreatic ductal adenocarcinoma; ubiquitination; ubiquitin-protein ligases; deubiquitinating enzymes; proteolysis-targeting chimeras
期刊名称：FRONTIERS IN MOLECULAR BIOSCIENCES （ 影响因子：5.0； 五年影响因子：5.2 ）
ISSN：
年卷期： 2023 年 10 卷
页码：
收录情况： SCI
摘要： Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.
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