The mechanism and biological function of non-canonical ubiquitination

<p indent="0mm">Ubiquitination is an energy-dependent post-translational modification that specifically modifies substrates. Due to its ability to modify numerous substrate proteins, it plays a crucial role in various cellular activities. With the deepening of research on canonical ubiquitination, non-canonical ubiquitination modifications have gradually been discovered and have attracted widespread attention. Non-canonical ubiquitination is a novel form of ubiquitin modification that differs from canonical ubiquitination in several aspects, including the types of amino acid residues of the substrate involved in the modification process, the linkage manner between ubiquitin and substrates, the types of substrates, and the enzymatic reaction processes. Non-canonical ubiquitination modifications can participate in regulating a multitude of biological activities such as host-pathogen interactions, autophagy, endoplasmic reticulum-associated degradation, and neuronal functions. This review summarizes the latest advancements in non-canonical ubiquitination research, discusses its mechanisms of action and biological functions within cells, and provides new perspectives for further understanding the complexity of ubiquitination modifications and their significance in life processes.