UFMylation System: An Emerging Player in Tumorigenesis

Simple Summary The ubiquitin-fold modifier 1 (UFM1) is a newly identified post-translational modification protein that has been implicated in multiple cellular processes and diseases. Noticeably, an aberrant UFM1 modification system has been closely related to various types of tumorigeneses, implying that the restoration of UFMylation homeostasis may serve as a promising therapeutic strategy. In this review, we summarize the structure, process and biological functions of the UFM1 modification system. In particular, we discuss the relationship between the UFMylation system and tumorigenesis, illustrating the underlying mechanisms and future perspectives. This article aims to improve our understanding of UFM1 modification, as well as provide some new strategies for cancer treatment. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule (UBLs), is evolutionarily expressed in multiple species except yeast. Similarly to ubiquitin, UFM1 is covalently attached to its substrates through a well-orchestrated three-step enzymatic reaction involving E1, the UFM1-activating enzyme (ubiquitin-like modifier-activating enzyme 5, UBA5); E2, the UFM1-conjugating enzyme 1 (UFC1); and E3, the UFM1-specific ligase 1 (UFL1). To date, numerous studies have shown that UFM1 modification is implicated in various cellular processes, including endoplasmic reticulum (ER) stress, DNA damage response and erythroid development. An abnormal UFM1 cascade is closely related to a variety of diseases, especially tumors. Herein, we summarize the process and functions of UFM1 modification, illustrating the relationship and mechanisms between aberrant UFMylation and diversified tumors, aiming to provide novel diagnostic biomarkers or therapeutic targets for cancer treatments.