Universität zu Köln

Kaehler, Christian, Isensee, Joerg ORCID: 0000-0002-3390-0051, Hucho, Tim ORCID: 0000-0002-4147-9308, Lehrach, Hans and Krobitsch, Sylvia (2014). 5-Fluorouracil affects assembly of stress granules based on RNA incorporation. Nucleic Acids Res., 42 (10). S. 6436 - 6448. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaehler, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Isensee, Joerg UNSPECIFIED orcid.org/0000-0002-3390-0051 UNSPECIFIED Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED Lehrach, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Krobitsch, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-449980
DOI:	10.1093/nar/gku264
Journal or Publication Title:	Nucleic Acids Res.
Volume:	42
Number:	10
Page Range:	S. 6436 - 6448
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1362-4962
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSLATION INITIATION; CARCINOMA-CELLS; MESSENGER-RNA; MECHANISM; YEAST; TIA-1; PHOSPHORYLATION; CYTOTOXICITY; RECRUITMENT; APOPTOSIS Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44998