This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Kammler, S. Articles by Jensen, T. H. PubMed PubMed Citation Articles by Kammler, S. Articles by Jensen, T. H.

---

DNA Damage and Cellular Stress Responses

The RNA Exosome Component hRrp6 Is a Target for 5-Fluorouracil in Human Cells

Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, University of Aarhus, Aarhus C., Denmark

Requests for reprints: Torben Heick Jensen, Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, University of Aarhus, C.F. Møllers Alle, Building 1130, 8000 Aarhus C., Denmark. Phone: 45-8942-2609; Fax: 45-8619-6500. E-mail: thj{at}mb.au.dk

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. (Mol Cancer Res 2008;6(6):990–5)

This article has been cited by other articles:

				M. Roberge Defining Drug Targets in Yeast Haploinsufficiency Screens: Application to Human Translational Pharmacology Sci. Signal., August 26, 2008; 1(34): pt5 - pt5. [Abstract] [Full Text] [PDF]