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PMID: 12640117 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

von Hippel-Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of cDNA arrays.

Molecular and cellular biology ·Vol. 23 ·No. 7 ·2003-04-00 ·Pages 2316-28

Galbán S, Fan J, Martindale JL, Cheadle C, Hoffman B, Woods MP, Temeles G, Brieger J, Decker J, Gorospe M

Abstract

Based on evidence that the von Hippel-Lindau (VHL) tumor suppressor protein is associated with polysomes and interacts with translation regulatory factors, we set out to investigate the potential influence of pVHL on protein translation. To this end, renal cell carcinoma (RCC) cells that either lacked pVHL or expressed pVHL through stable transfection were used to prepare RNA from cytosolic (unbound) and polysome-bound fractions. Hybridization of cDNA arrays using RNA from each fraction revealed a subset of transcripts whose abundance in polysomes decreased when pVHL function was restored. The tumor necrosis factor alpha (TNF-alpha) mRNA was identified as one of the transcripts that preferentially associated with polysomes in pVHL-deficient cells. Additional evidence that the TNF-alpha mRNA was a target of translational repression by pVHL was obtained from reporter gene assays, which further revealed that pVHL's inhibitory influence on protein synthesis occurred through the TNF-alpha 3'-untranslated region. Our findings uncover a novel function for the pVHL tumor suppressor protein as regulator of protein translation.

MeSH Terms
3' Untranslated Regions/physiology Blotting, Northern Carcinoma, Renal Cell/genetics,metabolism Cytosol/chemistry,metabolism Enzyme-Linked Immunosorbent Assay Gene Expression Profiling Gene Expression Regulation, Neoplastic/physiology Genes, Reporter Genes, Tumor Suppressor/physiology Humans Ligases/deficiency,genetics,metabolism Oligonucleotide Array Sequence Analysis Polyribosomes/chemistry,metabolism Protein Biosynthesis/physiology RNA, Messenger/analysis,metabolism Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha/biosynthesis,genetics Tumor Suppressor Proteins Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein
Chemicals
3' Untranslated Regions RNA, Messenger Tumor Necrosis Factor-alpha Tumor Suppressor Proteins Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein Ligases VHL protein, human
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Galbán Stefanie
Laboratory of Cellular and Molecular Biology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Fan Jinshui
Martindale Jennifer L
Cheadle Chris
Hoffman Bryan
Woods Michael P
Temeles Gretchen
Brieger Jürgen
Decker Jochen
Gorospe Myriam
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.7.2316-2328.2003
Published
2003-04-00
Pages
2316-28
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC150743
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.23.7.2316-2328.2003 PMC Full Text View journal details
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