Abstract
The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle
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Cell Cycle Proteins / metabolism
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Cell Line
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Cullin Proteins*
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Cyclin-Dependent Kinase Inhibitor Proteins
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Elongin
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F-Box Proteins*
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F-Box-WD Repeat-Containing Protein 7
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Fungal Proteins / metabolism
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Ligases*
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Liver
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Male
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Molecular Sequence Data
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Peptide Synthases / metabolism*
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Proteins / metabolism*
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Rats
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Rats, Sprague-Dawley
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Recombinant Fusion Proteins / metabolism
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S-Phase Kinase-Associated Proteins
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SKP Cullin F-Box Protein Ligases
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Transcription Factors / metabolism
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Tumor Suppressor Proteins*
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Ubiquitin-Protein Ligases*
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Ubiquitins / metabolism*
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Von Hippel-Lindau Tumor Suppressor Protein
Substances
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CDC4 protein, S cerevisiae
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CUL2 protein, human
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Carrier Proteins
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Cdc53 protein, S cerevisiae
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Cell Cycle Proteins
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Cullin Proteins
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Cyclin-Dependent Kinase Inhibitor Proteins
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ELOB protein, human
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ELOC protein, human
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Elob protein, rat
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Eloc protein, rat
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Elongin
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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FBXW7 protein, human
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Fungal Proteins
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Proteins
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Recombinant Fusion Proteins
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S-Phase Kinase-Associated Proteins
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SIC1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Tumor Suppressor Proteins
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Ubiquitins
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SKP Cullin F-Box Protein Ligases
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Ubiquitin-Protein Ligases
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Von Hippel-Lindau Tumor Suppressor Protein
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Ligases
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Peptide Synthases
Associated data
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GENBANK/AF140598
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GENBANK/AF140599