title: NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to proteasome for degradation through the P97UFD1/NPL4 complex.
abstract: 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.
authors.affiliation: From the State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Zhang
authors.forename: Ai-Xin
authors.initials: AX
authors.lastname: Song
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D000075687:NEDD8 Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*; D000074405:Valosin Containing Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C514112:NPLOC4 protein, human; C430242:NUB1 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; C491497:UFD1 protein, human; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Cullin 1; NEDD8; NUB1L; Neddylation; P97/VCp Complex; Proteasome; Protein Degradation; Protein Motifs; Protein-Protein Interactions; Ubiquitination
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