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  5-Fluorouracil affects assembly of stress granules based on RNA incorporation

Kähler, C., Isensee, J., Hucho, T., Lehrach, H., & Krobitsch, S. (2014). 5-Fluorouracil affects assembly of stress granules based on RNA incorporation. Nucleic Acids Research, 42(10), 6436-6447. doi:10.1093/nar/gku264.

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© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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 Creators:
Kähler, Christian1, Author              
Isensee, Jörg2, Author              
Hucho, Tim2, Author              
Lehrach, Hans3, Author              
Krobitsch, Sylvia1, Author              
Affiliations:
1Neurodegenerative Disorders (Sylvia Krobitsch), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479661              
2Signal Transduction in Mental Retardation and Pain (Tim Hucho), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479646              
3Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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 Abstract: The antimetabolite 5-fluorouracil is a widely used chemotherapeutic for the treatment of several solid cancers. However, resistance to 5-fluorouracil remains a major drawback in its clinical use. In this study we report that treatment of HeLa cells with 5-fluorouracil resulted in de novo assembly of stress granules. Moreover, we revealed that stress granule assembly under stress conditions as well as disassembly is altered in cells treated with 5-fluorouracil. Notably, we discovered that RACK1, a protein mediating cell survival and apoptosis, is a component of 5-fluorouracil-induced stress granules. To explore the mode of action of 5-fluorouracil accountable for de novo stress granule assembly, we analyzed 5-fluorouracil metabolites and noticed that stress granule assembly is caused by RNA, not DNA incorporating 5-fluorouracil metabolites. Interestingly, we observed that other RNA incorporating drugs also cause assembly of stress granules. Thus, our results suggest that incorporation of chemotherapeutics into RNA may result in stress granule assembly with potential significance in chemoresistance.

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Language(s): eng - English
 Dates: 2014-03-172014-03-202014-04-092014-06-01
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: Other: accessionPMC4041438
Other: pmcidPMC4041438
Other: pmc-uid4041438
PMID: 24728989
DOI: 10.1093/nar/gku264
URI: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4041438&tool=pmcentrez&rendertype=abstract
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Title: Nucleic Acids Research
Source Genre: Journal
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Publ. Info: Oxford University Press
Pages: - Volume / Issue: 42 (10) Sequence Number: - Start / End Page: 6436 - 6447 Identifier: Other: Nucleic Acids Res
Other: Nucleic Acids Res
Other: nar
Other: nar
ISSN: 0305-1048
ISSN: 1362-4962