Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans

ABSTRACT: The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated a subunits of hypoxia-inducible factor (HIF). Although studies of VHL defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF dependent and independent effects of VHL inactivation by studying gene expression patterns in C. elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1 independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17 and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1 independent function of VHL-1 that is connected with extracellular matrix function. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Bishop T, Lau KW, Epstein AC, Kim SK, Jiang M, O'rourke D, Pugh CW, Gleadle JM, Taylor MS, Hodgkin J, Ratcliffe PJ, Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans., Bishop T, et al. (2004) PLoS Biol 2(10):e289, 2004-10-01, http://biology.plosjournals.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020289 Computed

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Andrew Epstein

PROVIDER: E-GEOD-2963 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.

Bishop Tammie T Lau Kah Weng KW Epstein Andrew C R AC Kim Stuart K SK Jiang Min M O'Rourke Delia D Pugh Christopher W CW Gleadle Jonathan M JM Taylor Martin S MS Hodgkin Jonathan J Ratcliffe Peter J PJ

PLoS biology 20040907 10

The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated alpha subunits of hypoxia-inducible factor (HIF). Although studies of VHL-defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pat ...[more]

PMID: 15361934

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Dataset Information

Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans

Publications

Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.

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