fig 1 (IMAGE)
Caption
The UPS regulates the TME. (A) E1 ubiquitin-activating enzyme activates the carboxyl group of the C terminus of ubiquitin in an ATP-dependent manner through the formation of high-energy thioester bonds. Next, the ubiquitin molecule, which binds to E2, is moved to the targeting protein with the help of E3 ligase. Then, substrate protein labeled with ubiquitin enters into 26s proteasome for degradation, broken down into polypeptides and small-molecule amino acids. Deubiquitinase is to avoid degradation of substrate proteins by removing the ubiquitin tag from the substrate proteins. (B) UPS regulates tumor cells in the TME by regulating the levels of proteins related to the cell cycle, energy metabolism, and angiogenesis. (C) UPS regulates the anti-tumor immunity of T cells by regulating the protein levels of PD-1/PD-L1 and some inflammation-related cytokines. It also regulates the anti-tumor immunity of immune cells in the TME by regulating the maturation and anti-inflammatory presentation ability of DCs, the differentiation and their cytokines secretion of MDSCs, and the polarization of macrophages. (D) UPS modulates their role in tumor progression by regulating the lipid metabolism of adipocytes and the transformation and protein formation of CAFs. (E) UPS regulates tumor progression by regulating the levels of metalloproteinases and collagen in the TME. UPS, ubiquitin-proteasome system; TME, tumor microenvironment; PD-1/PD-L1, programmed death-1/ligand-1; DC, dendritic cell; PMN/M-MDSC, polymorphonuclear/monocytic-myeloid-derived suppressor cells; CAFs, cancer-associated fibroblasts; ICAM1, intercellular adhesion molecule 1.
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