SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation Journal Article


Authors: Kim, A. Y.; Bommelje, C. C.; Lee, B. E.; Yonekawa, Y.; Choi, L.; Morris, L. G.; Huang, G.; Kaufman, A.; Ryan, R. J. H.; Hao, B.; Ramanathan, Y.; Singh, B.
Article Title: SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation
Abstract: Covalent modification of cullins by the ubiquitin-like protein NEDD8 (neddylation) regulates protein ubiquitination by promoting the assembly of cullin-RING ligase E3 complexes. Like ubiquitination, neddylation results from an enzymatic cascade involving the sequential activity of a dedicated E1 (APPBP1/Uba3), E2 (Ubc12), and an ill-defined E3. We show that SCCRO (also known as DCUN1D1) binds to the components of the neddylation pathway (Cullin-ROC1, Ubc12, and CAND1) and augments but is not required for cullin neddylation in reactions using purified recombinant proteins.Wealso show that SCCRO recruits Ubc12∼NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation in purified protein assays. In contrast to findings in cellular systems where no binding is seen, we show that SCCRO and CAND1 can bind to the neddylated Cul1-ROC1 complex in assays using purified recombinant proteins. Although neddylated (not unneddylated) Cul1-ROC1 is released from CAND1 upon incubation with testis lysate from SCCRO+/+ mice, the addition of recombinant SCCRO is required to achieve the same results in lysate from SCCRO-/- mice. Combined, these results suggest that SCCRO is an important component of the neddylation E3 complex that functions to recruit charged E2 and is involved in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: controlled study; unclassified drug; human cell; nonhuman; ubiquitin; proteins; mouse; animals; mice; mice, knockout; mus; complex formation; hela cells; transcription factors; oncogene; ubiquitination; protein processing, post-translational; oncogene proteins; carrier proteins; recombinant proteins; protein secretion; multiprotein complexes; enzyme binding; ubiquitin-protein ligases; enzymes; cullin; cullin proteins; protein modification; ubiquitins; ligase; covalent modifications; cullins; neddylation; purification; cellular systems; complex assemblies; essential components; inhibitory effects; no bindings; purified proteins; sequential activities; cullin ring ligase; squamous cell carcinoma related oncogene; cell-free system
Journal Title: Journal of Biological Chemistry
Volume: 283
Issue: 48
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2008-11-28
Start Page: 33211
End Page: 33220
Language: English
DOI: 10.1074/jbc.M804440200
PUBMED: 18826954
PROVIDER: scopus
PMCID: PMC2586271
DOI/URL:
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: JBCHA" - "Source: Scopus"
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MSK Authors
  1. Russell J H Ryan
    5 Ryan
  2. Bhuvanesh Singh
    219 Singh
  3. Lydia Woo Young Choi
    5 Choi
  4. Alexander Y Kim
    2 Kim
  5. Luc Morris
    158 Morris
  6. Guochang Huang
    15 Huang
  7. Benjamin Lee
    3 Lee