TY - JOUR
T1 - Von Hippel-Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of cDNA arrays
AU - Galbán, Stefanie
AU - Fan, Jinshui
AU - Martindale, Jennifer L.
AU - Cheadle, Chris
AU - Hoffman, Bryan
AU - Woods, Michael P.
AU - Temeles, Gretchen
AU - Brieger, Jürgen
AU - Decker, Jochen
AU - Gorospel, Myriam
PY - 2003/4
Y1 - 2003/4
N2 - 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-α) mRNA was identified as one of the transcripts that preferentially associated with polysomes in pVHL-deficient cells. Additional evidence that the TNF-α 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-α 3′-untranslated region. Our findings uncover a novel function for the pVHL tumor suppressor protein as regulator of protein translation.
AB - 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-α) mRNA was identified as one of the transcripts that preferentially associated with polysomes in pVHL-deficient cells. Additional evidence that the TNF-α 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-α 3′-untranslated region. Our findings uncover a novel function for the pVHL tumor suppressor protein as regulator of protein translation.
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U2 - 10.1128/MCB.23.7.2316-2328.2003
DO - 10.1128/MCB.23.7.2316-2328.2003
M3 - Article
C2 - 12640117
AN - SCOPUS:0037377756
SN - 0270-7306
VL - 23
SP - 2316
EP - 2328
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 7
ER -