Defective in cullin neddylation 1 domain containing 1 (DCUN1D1)

Defective in cullin neddylation 1 domain containing 1 (DCUN1D1, also known as DCN1-like protein 1 or DCNL1) is a scaffold-type E3 ligase and a key regulatory component of the neddylation pathway, which conjugates the ubiquitin-like protein NEDD8 to cullin family proteins. DCUN1D1 facilitates neddylation by binding to cullin-RBX1 complexes, enhancing recruitment and orientation of the E2 enzyme UBC12 (UBE2M-NEDD8), and optimizing transfer of NEDD8 to cullins, promoting activation of cullin-RING E3 ubiquitin ligase complexes. It is involved in positive regulation of protein neddylation and ubiquitination, impacts protein degradation, and functions in the cytosol and nucleoplasm as part of the ubiquitin ligase complex. DCUN1D1 has been implicated in promoting carcinogenesis and is often overexpressed or altered in human cancers such as squamous cell carcinoma and glioma. The small-molecule DI-591 is a potent, selective inhibitor of the DCUN1D1–UBC12 interaction and has shown utility as a tool compound to probe cullin-3 neddylation-dependent pathways and potential therapeutic targeting.

Other names

DCUN1D1DCN1-like protein 1DCNL1

Inhibition of DCUN1D1–UBC12 interaction (e.g., by DI-591 blocks neddylation of cullin 3)