Publication Date:
1999-04-24
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamura, T -- Koepp, D M -- Conrad, M N -- Skowyra, D -- Moreland, R J -- Iliopoulos, O -- Lane, W S -- Kaelin, W G Jr -- Elledge, S J -- Conaway, R C -- Harper, J W -- Conaway, J W -- AG-11085/AG/NIA NIH HHS/ -- GM41628/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):657-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213691" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Carrier Proteins/chemistry/genetics/*metabolism
;
Cell Cycle
;
Cell Cycle Proteins/metabolism
;
Cell Line
;
*Cullin Proteins
;
Cyclin-Dependent Kinase Inhibitor Proteins
;
*F-Box Proteins
;
Fungal Proteins/metabolism
;
*Ligases
;
Liver
;
Male
;
Molecular Sequence Data
;
Peptide Synthases/*metabolism
;
Proteins/*metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Recombinant Fusion Proteins/metabolism
;
S-Phase Kinase-Associated Proteins
;
SKP Cullin F-Box Protein Ligases
;
Saccharomyces cerevisiae/metabolism
;
*Saccharomyces cerevisiae Proteins
;
Sequence Alignment
;
Transcription Factors/metabolism
;
*Tumor Suppressor Proteins
;
*Ubiquitin-Protein Ligases
;
Ubiquitins/*metabolism
;
Von Hippel-Lindau Tumor Suppressor Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
