Ubiquitination and SUMOylation: protein homeostasis control over cancer

Ubiquitination and SUMOylation are two essential components of the ubiquitination proteasome system playing fundamental roles in protein homeostasis maintenance and signal transduction, perturbation of which is associated with tumorigenesis. By comparing the mechanisms of ubiquitination and SUMOylation, assessing their crosstalk, reviewing their differential associations with cancer and identifying unaddressed yet important questions that may lead the field trend, this review sheds light on the similarities and differences of ubiquitination and SUMOylation toward the improved harnessing of both post-translational modification machineries, as well as forecasts novel onco-therapeutic opportunities through cell homeostasis control. Lay abstract Ubiquitination and SUMOylation are two key components of the ubiquitination-proteasome system, playing central roles in cancer initiation and development. Despite knowledge of these mechanisms and clinical efforts in developing proteasome inhibitors into onco-therapeutics, researchers are still questioning how the ubiquitination-proteasome system could be precisely harnessed in cancer control. Besides, the seemingly redundant roles played by ubiquitination and SUMOylation complicate the understanding of the roles of the ubiquitination-proteasome system in carcinogenesis. By comparing the mechanisms of ubiquitination and SUMOylation, reviewing their differential associations with cancer and identifying unaddressed yet important questions, this review sheds light on the similarities and differences of ubiquitination and SUMOylation and forecasts novel onco-therapeutic opportunities taking advantages of both machineries.

Automated summary

Ubiquitination and SUMOylation are essential components of the ubiquitination-proteasome system, playing central roles in cancer initiation and development. Researchers are still exploring how to precisely harness the ubiquitination-proteasome system in cancer control, while the seemingly redundant roles of ubiquitination and SUMOylation complicate the understanding of their roles in carcinogenesis. This review sheds light on the similarities and differences of ubiquitination and SUMOylation, forecasting novel onco-therapeutic opportunities through cell homeostasis control.