Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function.
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.
Mesh Terms:
Carrier Proteins, Cell Cycle Proteins, Cell Line, Cell Survival, Cullin Proteins, Fungal Proteins, Humans, Ligases, Mutation, Proteins, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Suppression, Genetic, Temperature, Transfection, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitins, Von Hippel-Lindau Tumor Suppressor Protein, Yeasts
Carrier Proteins, Cell Cycle Proteins, Cell Line, Cell Survival, Cullin Proteins, Fungal Proteins, Humans, Ligases, Mutation, Proteins, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Suppression, Genetic, Temperature, Transfection, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitins, Von Hippel-Lindau Tumor Suppressor Protein, Yeasts
Proc. Natl. Acad. Sci. U.S.A.
Date: May. 11, 1999
PubMed ID: 10318914
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