Emerging role of protein modification by UFM1 in cancer

Ubiquitin-fold modifier 1 (UFM1) is a newly identified ubiquitin-like protein. Like ubiquitin, UFM1 is conjugated to its target proteins through a three-step enzyme system: UBA5 (E1), UFC1 (E2), and UFL1 (E3), but with an additional essential component, UFBP1. This protein modification by UFM1 (ufmylation) can be reversed by UFM1-specific proteases (UFSPs). So far only a handful of target proteins for ufmylation have been identified, and they are mostly associated with either promotion or suppression of tumorigenesis. Here, we summarize the recent progress in the knowledge of tumor-suppressive and tumorigenic functions of ufmylation as well as in the development of therapeutic drugs against ufmylation-associated cancer.