Fig. 1

Neddylation, a complex multi-step process involving the post-translational attachment of the NEDD8 protein to target proteins, carries out various cellular functions and protein degradation. This process involves the maturation, activation, conjugation, ligation, and deneddylation stages and is conducted by specialized enzymes such as NEDP1, UBA3, and UBE2M. On the other hand, the neddylation modification significantly influences on the tumor microenvironment. This modification can impact various factors, including VEGF, PDGFB, ANGPT2, the EMT process, CAFs, and the ECM. Together, these two figures highlight the critical role of neddylation in both general cell function and the specific context of tumor progression. NEDD8, neural precursor cell expressed developmentally downregulated protein 8; UCH-L3, ubiquitin C-terminal hydrolase-L3; NEDP1, NEDD8 Protease 1; NAE1, NEDD8-activating enzyme 1; UBA3, ubiquitin-like modifier activating enzyme 3; UBE2 M/F, ubiquitin conjugating enzyme E2 M/F, CSN, COP9 signalosome; VEGF, vascular endothelial growth factor; PDGFB, platelet-derived growth factor B; ANGPT2, angiopoietin 2; EMT, epithelial-to-mesenchymal transition; CAFs, cancer-associated fibroblasts; ECM, extracellular matrix. Created with BioRender.com