Non-histone protein monoubiquitination: from cellular functions to mechanism and therapeutic potential of human diseases

Monoubiquitination, a widely occurring post-translational modification (PTM), is characterized by the attachment of a single ubiquitin to a lysine residue of the substrate via an isopeptide bond. In contrast to histone monoubiquitination, non-histone protein monoubiquitination plays critical roles in a broader range of cellular processes, including DNA damage response, transcriptional regulation, signal transduction, endocytic trafficking, autophagy, and immunity. Furthermore, emerging evidence has demonstrated that dysregulated monoubiquitination is involved in diverse human diseases. In this review, we provide a comprehensive overview of non-histone protein monoubiquitination from cellular functions to its mechanism and therapeutic implications for human diseases.