Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function

Proc Natl Acad Sci U S A. 1999 May 11;96(10):5510-5. doi: 10.1073/pnas.96.10.5510.


The von Hippel-Lindau tumor suppressor protein pVHL assembles with cullin-2 (hCUL-2) and elongin B/C forming a protein complex, CBCVHL, that resembles SKP1-CDC53-F-box protein ubiquitin ligases. Here, we show that hCUL-2 is modified by the conserved ubiquitin-like protein NEDD8 and that NEDD8-hCUL-2 conjugates are part of CBCVHL complexes in vivo. Remarkably, the formation of these conjugates is stimulated by the pVHL tumor suppressor. A tumorigenic pVHL variant, however, is essentially deficient in this activity. Thus, ligation of NEDD8 to hCUL-2 is linked to pVHL activity and may be important for pVHL tumor suppressor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Survival
  • Cullin Proteins*
  • Fungal Proteins / metabolism
  • Humans
  • Ligases / metabolism
  • Mutation
  • NEDD8 Protein
  • Proteins / genetics*
  • Recombinant Proteins / genetics
  • Saccharomyces cerevisiae Proteins*
  • Suppression, Genetic*
  • Temperature
  • Transfection
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Ubiquitins / metabolism*
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Yeasts


  • CUL2 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cullin 1
  • Cullin Proteins
  • Fungal Proteins
  • NEDD8 Protein
  • NEDD8 protein, human
  • Proteins
  • RUB1 protein, S cerevisiae
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Tumor Suppressor Proteins
  • Ubiquitins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human