NEDD8 Ultimate Buster-1 Long (NUB1L) Protein Promotes Transfer of NEDD8 to Proteasome for Degradation through the P97UFD1/NPL4 Complex
Copyright policy )NEDD8 Ultimate Buster-1 Long (NUB1L) Protein Promotes Transfer of NEDD8 to Proteasome for Degradation through the P97UFD1/NPL4 Complex
The NEDD8 protein and neddylation levels in cells are modulated by NUB1L or NUB1 through proteasomal degradation, but the underlying molecular mechanism is not well understood. Here, we report that NUB1L down-regulated the protein levels of NEDD8 and neddylation through specifically recognizing NEDD8 and P97/VCP. NUB1L directly interacted with NEDD8, but not with ubiquitin, on the key residue Asn-51 of NEDD8 and with P97/VCP on its positively charged VCP binding motif. In coordination with the P97-UFD1-NPL4 complex (P97(UFD1/NPL4)), NUB1L promotes transfer of NEDD8 to proteasome for degradation. This mechanism is also exemplified by the canonical neddylation of cullin 1 for SCF (SKP1-cullin1-F-box) ubiquitin E3 ligases that is exquisitely regulated by the turnover of NEDD8.
- Medical Research Council United Kingdom
- Chinese Academy of Sciences China (People's Republic of)
- Center for Excellence in Molecular Cell Science China (People's Republic of)
- MRC Laboratory of Molecular Biology United Kingdom
- Shanghai Institutes for Biological Sciences China (People's Republic of)
Adenosine Triphosphatases, Proteasome Endopeptidase Complex, SKP Cullin F-Box Protein Ligases, NEDD8 Protein, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Proteins, Cell Cycle Proteins, Cullin Proteins, Cell Line, Adaptor Proteins, Vesicular Transport, Valosin Containing Protein, Multiprotein Complexes, Proteolysis, Humans, Ubiquitins, Adaptor Proteins, Signal Transducing, Transcription Factors
Adenosine Triphosphatases, Proteasome Endopeptidase Complex, SKP Cullin F-Box Protein Ligases, NEDD8 Protein, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Proteins, Cell Cycle Proteins, Cullin Proteins, Cell Line, Adaptor Proteins, Vesicular Transport, Valosin Containing Protein, Multiprotein Complexes, Proteolysis, Humans, Ubiquitins, Adaptor Proteins, Signal Transducing, Transcription Factors
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