fig 2 (IMAGE)
Caption
UPS regulates tumor cells. (A) E3 ubiquitin ligases APC/C and SCF regulate the cell cycle. MDM2, as a classical ubiquitin ligase, regulates p53 to regulate the cell cycle, while TRIM2, another E3 ligase, competes with it. Other ubiquitin ligases such as Cul4a, TRIM28, and RNF2 also regulate MDM2 ubiquitin ligase, which indirectly regulates p53 protein stability. In addition, several ubiquitin ligases including CHIP, TRIM24, TRAF6, and TRAF7 can also regulate p53. (B) TRIM25, FBP1, RNF167, and TRIM22 regulate the mTOR signaling pathway by modulating PTEN, FBXW7, sestrin2, and RNF2, respectively, which ultimately regulates energy metabolism in tumor cells. (C, D) HIF-1α is regulated by different ubiquitin proteases under hypoxia and normoxia conditions respectively. APC/C, anaphase-promoting complex/cyclosome; CDC20, cell division cycle 20; SCF, Skp1-Cul1-F-box; CDH1, E-Cadherin; SKP, S-phase kinase-associated protein; TRIM, tripartite motif-containing; MDM, mouse double minute; RBX/RNF, RING finger protein; CRL, cullin-RING E3 ubiquitin ligase; USP, ubiquitin-specific protease; OTU, ovarian tumor proteases; mTOR, mechanistic target of rapamycin complex; FBXW, F-Box, and WD repeat domain containing; FBP1, fructose-bisphosphatase 1; UCH, ubiquitin carboxy-terminal hydrolases; VHL, Von Hippel-Lindau protein; HIF, hypoxia-inducible transcription factor; UBE2K, ubiquitin-conjugating enzyme E2K; MAEA, macrophage-erythroblast attacher; VEGF, vascular endothelial growth factor; DUB, deubiquitinase; TRAF, tumor necrosis factor receptor-associated factor.
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