Abstract
Ubiquitin-conjugating enzymes (E2s) are one of the three enzymes required by the ubiquitin-proteasome pathway to connect activated ubiquitin to target proteins via ubiquitin ligases. E2s determine the connection type of the ubiquitin chains, and different types of ubiquitin chains regulate the stability and activity of substrate proteins. Thus, E2s participate in the regulation of a variety of biological processes. In recent years, the importance of E2s in human health and diseases has been particularly emphasized. Studies have shown that E2s are dysregulated in variety of cancers, thus it might be a potential therapeutic target. However, the molecular basis of E2s as a therapeutic target has not been described systematically. We reviewed this issue from the perspective of the special position and role of E2s in the ubiquitin-proteasome pathway, the structure of E2s and biological processes they are involved in. In addition, the inhibitors and microRNAs targeting E2s are also summarized. This article not only provides a direction for the development of effective drugs but also lays a foundation for further study on this enzyme in the future.
Highlights
The 2004 Nobel Prize in Chemistry was awarded to three scientists (Aron Ciechanover, Avaram Heshko and Irwin Rose) for their discovery of the mechanism of protein degradation regulated by ubiquitin (Ub)
The UBE2C mRNA or protein can hardly be detected in normal tissues; it is abnormally elevated in diseases such as cerebral cancer, lung cancer (LC), leukemia, lymphoma, gastric cancer (GC), breast cancer (BC), colon cancer (CC) and hepatocellular carcinoma (HCC) [6,7,8,9]
Wu et al [11] found that UBE2N is related to the low overall survival rate of human BC and is directly involved in the process of metastasis, which is necessary for lung colonization and the survival and proliferation of established metastatic lesions
Summary
The 2004 Nobel Prize in Chemistry was awarded to three scientists (Aron Ciechanover, Avaram Heshko and Irwin Rose) for their discovery of the mechanism of protein degradation regulated by ubiquitin (Ub) They found the same class of peptides in mammals, bacteria and plants, whose structures and properties were very similar. Cases of the abnormal expression of other E2 members in different cancer cells or tissues are widespread This affects the protein turnover of cancer cells, and indirectly regulates the proliferation, metastasis, anti-apoptosis and drug resistance of cancer cells by participating in certain biological processes. We discuss the molecular basis of E2s as a target for cancer therapy from the special position and functions of E2s in UPP, the structure of E2s and biological processes they are participated in, and the efforts made to develop corresponding inhibitors. Researchers can select E2 as a specific target and consider the possible positive and negative effects according to the biological processes it participates in, allowing them to develop effective inhibitors with few side effects to control the occurrence and development of cancer
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