English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  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 (London), 42(10), 6436-6447. doi:10.1093/nar/gku264.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-7808-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-7809-C
Genre: Journal Article

Files

show Files
hide Files
:
Kaehler.pdf (Publisher version), 9MB
Name:
Kaehler.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 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              

Content

show
hide
Free keywords: Antimetabolites, Antineoplastic/metabolism/*pharmacology Azacitidine/metabolism Cell Line DNA/metabolism Eukaryotic Initiation Factor-2/metabolism Fluorouracil/metabolism/*pharmacology GTP-Binding Proteins/analysis HeLa Cells Humans Neoplasm Proteins/analysis Oxidative Stress RNA/*metabolism Receptors, Cell Surface/analysis Ribonucleoproteins/analysis/*metabolism *Stress, Physiological Thioguanine/metabolism
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2014-04-112014-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1093/nar/gku264
ISSN: 1362-4962 (Electronic)0305-1048 (Print)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nucleic Acids Research (London)
  Other : Nucleic Acids Res
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 42 (10) Sequence Number: - Start / End Page: 6436 - 6447 Identifier: ISSN: 0305-1048
CoNE: https://pure.mpg.de/cone/journals/resource/110992357379342