title: Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.
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.
authors.affiliation: Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kamura
authors.forename: D M
authors.initials: DM
authors.lastname: Koepp
authors.forename: M N
authors.initials: MN
authors.lastname: Conrad
authors.forename: D
authors.initials: D
authors.lastname: Skowyra
authors.forename: R J
authors.initials: RJ
authors.lastname: Moreland
authors.forename: O
authors.initials: O
authors.lastname: Iliopoulos
authors.forename: W S
authors.initials: WS
authors.lastname: Lane
authors.forename: W G
authors.initials: WG
authors.lastname: Kaelin
authors.forename: S J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: R C
authors.initials: RC
authors.lastname: Conaway
authors.forename: J W
authors.initials: JW
authors.lastname: Harper
authors.forename: J W
authors.initials: JW
authors.lastname: Conaway
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D044842:Cullin Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D000075065:Elongin; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D005656:Fungal Proteins / Q000378:metabolism; D008025:Ligases; D008099:Liver; D008297:Male; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: C080443:CDC4 protein, S cerevisiae; C105153:CUL2 protein, human; D002352:Carrier Proteins; C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C000616396:ELOB protein, human; C000616395:ELOC protein, human; C000616402:Elob protein, rat; C000616400:Eloc protein, rat; D000075065:Elongin; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D005656:Fungal Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D044786:S-Phase Kinase-Associated Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; D010453:Peptide Synthases