Skip to main content
  • Oral presentation
  • Open access
  • Published:

A novel NEDD8-binding protein modulates NF-κB signaling pathway

In canonical NF-κB signaling pathway, a ubiquitin ligase called SCF (S kp1, C ul1, F-box protein) complex is essential for I-κB degradation. The activity of the SCF complex is positively regulated by a post-translational modification of Cul1 subunit with a ubiquitin-like protein NEDD8. Like ubiquitin, NEDD8 possesses evolutionary conserved Lys residues on its surface, and forms poly-NEDD8 chain in vivo and in vitro [1, 2]. Despite the importance of the NEDD8 modification in all eukaryotic cells, little is known about the function of poly-NEDD8 chain. To elucidate the function of the poly-NEDD8 chain in vivo, we screened p oly-N EDD8 chain b inding p roteins (PNBPs) using a yeast two-hybrid system. Of the identified PNBPs, PNBP1 was identical to a gene present in non-HLA celiac disease and rheumatoid arthritis risk loci [3].

PNBP1 interacted with NEDD8, NEDD8-conjugating enzyme Ubc12 and Cul1. PNBP1 strongly associated with wild-type Cul1, but not its NEDDylation defective Cul1(K720R) mutant, suggesting that the interaction is mediated in part through NEDD8. Furthermore, PNBP1 promoted NEDDylation of Cul1 in an in vitro reconstitution assay. These activities were dependent on RING-finger domain of PNBP1. Finally, knockdown of PNBP1 led to reduction of the NF-κB activation, suggesting that PNBP1 is an important modulator of the NF-κB signaling pathway.


  1. Jones J, Wu K, Yang Y, Guerrero C, Nillegoda N, Pan ZQ, Huang L: A targeted proteomic analysis of the ubiquitin-like modifier NEDDD8 and associated proteins. J Proteome Res. 2008, 7: 1274-1287. 10.1021/pr700749v.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Ohki Y, Funatsu N, Konishi N, Chiba T: The mechanism of poly-NEDD8 chain formation in vitro. Biochem Biophys Res Commun. 2009, 381: 443-447. 10.1016/j.bbrc.2009.02.090.

    Article  CAS  PubMed  Google Scholar 

  3. Alexandra Zhernakova A, et al: Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PloS Genet. 2011, 7: e10020004-

    Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Takashima, O., Tsuruta, F., Ebina, M. et al. A novel NEDD8-binding protein modulates NF-κB signaling pathway. Arthritis Res Ther 14 (Suppl 1), O46 (2012).

Download citation

  • Published:

  • DOI: