The Post-Translational Role of UFMylation in Physiology and Disease

Ubiquitin-fold modifier 1 (UFM1) is a newly identified ubiquitin-like protein that has been conserved during the evolution of multicellular organisms. In a similar manner to ubiquitin, UFM1 can become covalently linked to the lysine residue of a substrate via a dedicated enzymatic cascade. Although a limited number of substrates have been identified so far, UFM1 modification (UFMylation) has been demonstrated to play a vital role in a variety of cellular activities, including mammalian development, ribosome biogenesis, the DNA damage response, endoplasmic reticulum stress responses, immune responses, and tumorigenesis. In this review, we summarize what is known about the UFM1 enzymatic cascade and its biological functions, and discuss its recently identified substrates. We also explore the pathological role of UFMylation in human disease and the corresponding potential therapeutic targets and strategies.