Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.
NEDD8 is a ubiquitin-like protein that controls vital biological events through its conjugation to cullin family members. Recently, we identified a negative regulator of the NEDD8 conjugation system, NUB1, which interacts with NEDD8 and down-regulates NEDD8 expression post-transcriptionally (Kito, K., Yeh, E. T. H., and Kamitani, T. (2001) J. Biol. ... Chem. 276, 20603-20609). Here, we show that NUB1 possesses a ubiquitin-like domain at the N-terminal region and binds to S5a of the 19 S proteasome activator (PA700). A GST pull-down assay revealed that the overexpression of NUB1 leads to a greater precipitation of NEDD8 conjugates with GST-S5a, suggesting that NUB1 might have an adaptor function between S5a and NEDD8. Furthermore, proteasome inhibitors completely block NUB1-mediated down-regulation of NEDD8 expression. These results suggest that NUB1 recruits NEDD8 and its conjugates to the proteasome for degradation, providing a direct functional link between the NEDD8 conjugation system and the proteasomal degradation pathway.
Mesh Terms:
Animals, Blotting, Western, COS Cells, Cysteine Endopeptidases, Glutathione Transferase, Humans, Hydrolysis, Multienzyme Complexes, Proteasome Endopeptidase Complex, Protein Binding, Transcription Factors, Tumor Cells, Cultured, Ubiquitins
Animals, Blotting, Western, COS Cells, Cysteine Endopeptidases, Glutathione Transferase, Humans, Hydrolysis, Multienzyme Complexes, Proteasome Endopeptidase Complex, Protein Binding, Transcription Factors, Tumor Cells, Cultured, Ubiquitins
J. Biol. Chem.
Date: Dec. 07, 2001
PubMed ID: 11585840
View in: Pubmed Google Scholar
Download Curated Data For This Publication
10620
Switch View:
- Interactions 3