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Mol Cancer Res. 2008 Jun;6(6):990-5. doi: 10.1158/1541-7786.MCR-07-2217.

The RNA exosome component hRrp6 is a target for 5-fluorouracil in human cells.

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1
Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, University of Aarhus, CF Møllers Alle, Building 1130, 8000 Aarhus C., Denmark.

Abstract

The drug 5-fluorouracil (5-FU) is a widely used chemotherapeutic in the treatment of solid tumors. Recently, the essential 3'-5' exonucleolytic multisubunit RNA exosome was implicated as a target for 5-FU in yeast. Here, we show that this is also the case in human cells. HeLa cells depleted of the inessential exosome component hRrp6, also called PM/Scl100, are significantly growth impaired relative to control cells after 5-FU administration. The selective stabilization of bona fide hRrp6 RNA substrates on 5-FU treatment suggests that this exosome component is specifically targeted. Consistently, levels of hRrp6 substrates are increased in two 5-FU-sensitive cell lines. Interestingly, whereas down-regulation of all tested core exosome components results in decreased hRrp6 levels, depletion of hRrp6 leaves levels of other exosome components unchanged. Taken together, our data position hRrp6 as a promising target for antiproliferative intervention.

PMID:
18567802
DOI:
10.1158/1541-7786.MCR-07-2217
[Indexed for MEDLINE]
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