Abstract
The ubiquitin-mediated degradation system is responsible for controlling various tumor-promoting processes, including DNA repair, cell cycle arrest, cell proliferation, apoptosis, angiogenesis, migration and invasion, metastasis, and drug resistance. The conjugation of ubiquitin to a target protein is mediated sequentially by the E1 (activating)‒E2 (conjugating)‒E3 (ligating) enzyme cascade. Thus, E2 enzymes act as the central players in the ubiquitination system, modulating various pathophysiological processes in the tumor microenvironment. In this review, we summarize the types and functions of E2s in various types of cancer and discuss the possibility of E2s as targets of anticancer therapeutic strategies.
Highlights
Despite significant progress made in the therapies for cancer, cancer is the second leading cause of death worldwide, accounting for an estimated 10 million deaths in 2020 according to a World Health Organization report
Is overexpressed in 27 cancers, and that its overexpression correlates with worse overall survival (OS) [30]. These findings provide evidence that UBE2C acts as a proto-oncogene and can be considered as a therapeutic target for most cancers
UBE2F was upregulated by platinum chemotherapy and its knockdown sensitized lung cancer cells to platinum treatment by elevating NOXA protein levels and stimulating cell apoptosis [42]. These findings indicate that UBE2F might be a promising target for lung cancer-targeting therapeutics and for sensitizing lung cancer cells to platinum-based chemotherapy
Summary
Despite significant progress made in the therapies for cancer, cancer is the second leading cause of death worldwide, accounting for an estimated 10 million deaths in 2020 according to a World Health Organization report (https://www.who.int/news-room/factsheets/detail/cancer, accessed on 3 March 2021). Depending outcome of protein degradation ubiquitination, thesubstrate, fates of substrates will be peptide(5). Which is not recognized by the proteasome, resulting in altered function of the substrate protein, such as DNA repair, translation, and endocytosis. Different E2s may dictate different types of Ub linkage and the extent of commonly governs cellular processes, such as DNA repair, translation, inflammation, and. Given the critical E2 enzymes are involved in various tumor-promoting processes, including repair, apoprole of ubiquitination in controlling the fates of the substrates and the pivotal role of E2tosis, cell cycle progression, and oncogenic signaling pathways. Given the critical role conjugating enzymes in the E1–E2–E3 Ub transfer cascade, we summarize the current ofknowledge ubiquitination controlling the fates of the substrates the pivotal role ofinE2on theinroles of Ub-conjugating enzymes in signal and transduction pathways conjugating enzymes indiscuss the E1–E2–E3. Knowledge on the roles of Ub-conjugating enzymes in signal transduction pathways in cancer progression and discuss the possibility of E2s as targets in cancer therapies
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