Non-proteolytic ubiquitylation in cellular signaling and human disease

Ubiquitylation is one of the most common post-translational modifications (PTMs) of proteins that frequently targets substrates for proteasomal degradation. However it can also result in non-proteolytic events which play important functions in cellular processes such as intracellular signaling, membrane trafficking, DNA repair and cell cycle. Emerging evidence demonstrates that dysfunction of non-proteolytic ubiquitylation is associated with the development of multiple human diseases. In this review, we summarize the current knowledge and the latest concepts on how non-proteolytic ubiquitylation pathways are involved in cellular signaling and in disease-mediating processes. Our review, may advance our understanding of the non-degradative ubiquitylation process.