Ubiquitin signaling in pancreatic ductal adenocarcinoma

Shengnan Lv; Jian Zhang; Xinyu Peng; Huan Liu; Yan Liu; Feng Wei

doi:10.3389/fmolb.2023.1304639

Ubiquitin signaling in pancreatic ductal adenocarcinoma

Front Mol Biosci. 2023 Dec 20:10:1304639. doi: 10.3389/fmolb.2023.1304639. eCollection 2023.

Authors

Shengnan Lv¹, Jian Zhang¹, Xinyu Peng¹, Huan Liu¹, Yan Liu², Feng Wei¹

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
² Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.

Abstract

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.

Keywords: deubiquitinating enzymes; pancreatic ductal adenocarcinoma; proteolysis-targeting chimeras; ubiquitination; ubiquitin–protein ligases.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (81972273 and 82273276) and the Natural Science Foundation of Jilin Province (20200201546JC).