Home LiteratureArticle Details

PMID: 10213691 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.

Science (New York, N.Y.) ·Vol. 284 ·No. 5414 ·1999-04-23 ·Pages 657-61

Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG, Elledge SJ, Conaway RC, Harper JW, Conaway JW

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.

MeSH Terms

Amino Acid Sequence Animals Carrier Proteins/chemistry,genetics,metabolism Cell Cycle Cell Cycle Proteins/metabolism Cell Line Cullin Proteins Cyclin-Dependent Kinase Inhibitor Proteins Elongin F-Box Proteins F-Box-WD Repeat-Containing Protein 7 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

Chemicals

CDC4 protein, S cerevisiae CUL2 protein, human Carrier Proteins Cdc53 protein, S cerevisiae Cell Cycle Proteins Cullin Proteins Cyclin-Dependent Kinase Inhibitor Proteins ELOB protein, human ELOC protein, human Elob protein, rat Eloc protein, rat Elongin F-Box Proteins F-Box-WD Repeat-Containing Protein 7 FBXW7 protein, human Fungal Proteins Proteins Recombinant Fusion Proteins S-Phase Kinase-Associated Proteins SIC1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors Tumor Suppressor Proteins Ubiquitins SKP Cullin F-Box Protein Ligases Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein Ligases Peptide Synthases

Authors & Affiliations

12 authors, click to expand affiliations / ORCID

Kamura T

Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Koepp D M

Conrad M N

Skowyra D

Moreland R J

Iliopoulos O

Lane W S

Kaelin W G

Elledge S J

Conaway R C

Harper J W

Conaway J W

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.284.5414.657

Published

1999-04-23

Pages

657-61

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NIA NIH HHS · AG-11085 · United States

NIGMS NIH HHS · GM41628 · United States

Databases

GENBANK

AF140598, AF140599

Corrections

CommentIn

PMID: 10328744

External Links

PubMed source DOI: 10.1126/science.284.5414.657 View journal details

Analysis Services

Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.

Contact

WeChat Official Account