E2 ubiquitin-conjugating enzymes in cancer: Implications for immunotherapeutic interventions

Abstract

Despite the medical advances of the 21st century, the incidence of cancer continues to increase and the search for a universal cure remains a major health challenge. Our lack of understanding the complex pathophysiology of the tumor microenvironment has hindered the development and efficiency of anti-cancer therapeutic strategies. The tumor microenvironment, composed of multiple cellular and non-cellular components, enables tumorpromoting processes such as proliferation, angiogenesis, migration and invasion, metastasis, and drug resistance. The ubiquitin-mediated degradation system is involved in several physiologic processes including cell cycling, signal transduction, receptor downregulation, endocytosis and transcriptional regulation. Ubiquitination includes attachment of ubiquitin to target proteins via E1 (activating), E2 (conjugating) and E3 (ligating) enzymes. Several studies have shown that E2 enzymes are dysregulated in variety of cancers. Multiple investigations have demonstrated the involvement of E2s in various tumor-promoting processes including DNA repair, cell cycle progression, apoptosis and oncogenic signaling. E2 enzymes consist of 40 members that facilitate ubiquitinsubstrate conjugation thereby modulating the stability and interaction of various proteins. As such, E2s are potential biomarkers as diagnostic, prognostic and therapeutic tools. In this review, we discuss the role of E2s in modulating various types of cancer.

Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

“…E2-conjugating enzymes play a central role in the formation and progression of various tumors [30]. Although the role of some UBE2 members in OC has been con rmed, to our knowledge, no studies have comprehensively analyzed the prognostic value and functional mechanism of the UBE2 family in OC.…”

“…Growing evidence is being provided that the interaction between immune and cancer cells in the tumor microenvironment has an impact on tumor progression [30]. OC is an immunogenic tumor that can be recognized and attacked by the immune system.…”

Increased expression of UBE2T predicting poor survival of ovarian cancer: based on bioinformatics analysis of UBE2s, clinical samples and the GEO database

“…Growing evidence is being provided that the interaction between immune and cancer cells in the tumor microenvironment has an impact on tumor progression [4]. Ovarian cancer is an immunogenic tumor that can be recognized and attacked by the immune system.…”

“…These enzymes include ubiquitin-activating (UBE1), ubiquitin-conjugating (UBE2), and ubiquitin-ligating (UBE3) enzymes, which facilitate ubiquitination and lead to proteasome-mediated protein degradation [4].…”

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

“…Interestingly, apart from E3 ligases, the aberrant expressions and critical functions of ubiquitinconjugating enzymes, being considered as a family of constitutive enzymes before, in tumorigenesis have been indicated by the recent work [7].…”