Ubiquitination and SUMOylation: Protein Homeostasis Control Over Cancer

Abstract

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.

Keywords::

• cancer
• protein homeostasis
• SUMOylation
• ubiquitination

Author contributions

X Dai conceptualized the idea, drafted the manuscript and provided the financial support. T Zhang contributed in literature searching and figure preparation. D Hua finalized the manuscript by providing additional insights.

Financial & competing interests disclosure

This study was funded by the National Natural Science Foundation of China (grant no. 81972789), Fundamental Research Funds for the Central Universities (grant no. JUSRP22011) and Technology Development Funding of Wuxi (grant no. WX18IVJN017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was funded by the National Natural Science Foundation of China (grant no. 81972789), Fundamental Research Funds for the Central Universities (grant no. JUSRP22011) and Technology Development Funding of Wuxi (grant no. WX18IVJN017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.