SCCRO (DCUN1D1) promotes nuclear translocation and assembly of the neddylation E3 complex Journal Article

Authors: Huang, G.; Kaufman, A. J.; Ramanathan, Y.; Singh, B.
Article Title: SCCRO (DCUN1D1) promotes nuclear translocation and assembly of the neddylation E3 complex
Abstract: SCCRO/DCUN1D1/DCN1 (squamous cell carcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin neddylation) serves as an accessory E3 in neddylation by binding to cullin and Ubc12 to allow efficient transfer of Nedd8. In this work we show that SCCRO has broader, pleiotropic effects that are essential for cullin neddylation in vivo. Reduced primary nuclear localization of Cul1 accompanying decreased neddylation and proliferation in SCCRO-/- mouse embryonic fibroblasts led us to investigate whether compartmentalization plays a regulatory role. Decreased nuclear localization, neddylation, and defective proliferation in SCCRO -/- mouse embryonic fibroblasts were rescued by transgenic expression of SCCRO. Expression of reciprocal SCCRO and Cul1-binding mutants confirmed the requirement forSCCRO in nuclear translocation and neddylation of cullins in vivo. Nuclear translocation of Cul1 by tagging with a nuclear localization sequence allowed neddylation independent of SCCRO, but at a lower level. We found that in the nucleus, SCCRO enhances recruitment of Ubc12 to Cul1 to promote neddylation. These findings suggest thatSCCROhasanessential role in neddylation in vivo involving nuclear localization of neddylation components and recruitment and proper positioning of Ubc12. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: controlled study; protein expression; gene translocation; squamous cell carcinoma; nonhuman; protein localization; cell proliferation; animal cell; mouse; protein assembly; protein binding; oncogene; cell culture; immunoprecipitation; transgene; fibroblast; fibroblasts; cellular distribution; in-vivo; fractionation; ubiquitin protein ligase e3; cullin; protein modification; nuclear localization; binding mutant; cullins; mouse embryonic fibroblasts; nuclear localization sequences; nuclear translocations; pleiotropic effects; transgenic expression; neddylation; oncogene sccro
Journal Title: Journal of Biological Chemistry
Volume: 286
Issue: 12
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2011-03-25
Start Page: 10297
End Page: 10304
Language: English
DOI: 10.1074/jbc.M110.203729
PROVIDER: scopus
PMCID: PMC3060484
PUBMED: 21247897
Notes: --- - "Export Date: 23 June 2011" - "CODEN: JBCHA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Bhuvanesh Singh
    219 Singh
  2. Guochang Huang
    15 Huang