Results indicate that neddylation contributes to reactivating HIV provirus transcription and antigen expression, as well as enhancing infectivity of resulting virions. This suggests hypotheses to test...

(Cell Stem Cell 31, 1162–1174.e1–e9; August 1, 2024)

DNA polymerase eta (Pol η) is a Y-family translesion polymerase responsible for synthesizing new DNA across UV-damaged templates. It is recruited to replication forks following mono-ubiquitination of ...

Abstract. DNA polymerase eta (Pol η) is a Y-family translesion polymerase responsible for synthesizing new DNA across UV-damaged templates. It is recruited

Oncogene - RNF187 neddylation in pancreatic cancer activates malignancy via IQGAP1-dependent actin cytoskeleton rearrangement

Read the full paper: UBE2M-mediated EGFR neddylation drives keratinocyte proliferation in psoriasis

Protein neddylation modification involves transfer of neural precursor cell expressed developmentally downregulated protein 8 (NEDD8), a ubiquitin-like protein, to substrates through a three-step enzymatic cascade mediated by NEDD8-activating enzyme (NAE), conjugating enzyme and ligases. Given Cullin-RING ligases (CRLs) as the uppermost substrates which regulate degradation of numerous proteins, neddylation modulates numerous biological functions, including tumor development. MLN4924, a potent NAE inhibitor, has emerged as a promising anti-cancer agent based on neddylation interference. However, resistance to MLN4924 poses a significant challenge. Growing evidence suggests that neddylation directly and indirectly modulates the tumor immune microenvironment (TIME), providing novel insights into its impact on tumor dynamics and the development of resistance to MLN4924. This understanding indicates that targeting neddylation could potentially be combined with immunotherapies for more effective treatment strategies. Here, we briefly outline how neddylation is organized and its modulatory roles in both tumor cells and intertumoral immune cells, proposing an optimistic outlook for neddylation-targeted therapy.

(Cell Stem Cell 31, 1162–1174.e1–e9; August 1, 2024)

Read the full paper: The inner nuclear membrane protein SUN1 regulates cullin-3 neddylation to maintain insulin signaling

Read the full paper: Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration

Protein neddylation modification involves transfer of neural precursor cell expressed developmentally downregulated protein 8 (NEDD8), a ubiquitin-like protein, to substrates through a three-step enzymatic cascade mediated by NEDD8-activating enzyme (NAE), conjugating enzyme and ligases. Given Cullin-RING ligases (CRLs) as the uppermost substrates which regulate degradation of numerous proteins, neddylation modulates numerous biological functions, including tumor development. MLN4924, a potent NAE inhibitor, has emerged as a promising anti-cancer agent based on neddylation interference. However, resistance to MLN4924 poses a significant challenge. Growing evidence suggests that neddylation directly and indirectly modulates the tumor immune microenvironment (TIME), providing novel insights into its impact on tumor dynamics and the development of resistance to MLN4924. This understanding indicates that targeting neddylation could potentially be combined with immunotherapies for more effective treatment strategies. Here, we briefly outline how neddylation is organized and its modulatory roles in both tumor cells and intertumoral immune cells, proposing an optimistic outlook for neddylation-targeted therapy.

Read the full paper: Neddylation E1 Obligatory Subunit Nae1 Is Critical to Neuromuscular Junction Development and Maintenance