| Role of the sub-cellular localization of RasGAP fragment N2 for its ability to sensitize cancer cells to genotoxin-induced apoptosis. | |
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MedLine Citation:
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PMID: 19328779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The specific sensitization of tumor cells to the apoptotic response induced by genotoxins is a promising way of increasing the efficacy of chemotherapies. The RasGAP-derived fragment N2, while not regulating apoptosis in normal cells, potently sensitizes tumor cells to cisplatin- and other genotoxin-induced cell death. Here we show that fragment N2 in living cells is mainly located in the cytoplasm and only minimally associated with specific organelles. The cytoplasmic localization of fragment N2 was required for its cisplatin-sensitization property because targeting it to the mitochondria or the ER abrogated its ability to increase the death of tumor cells in response to cisplatin. These results indicate that fragment N2 requires a spatially constrained cellular location to exert its anti-cancer activity. |
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Authors:
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Alessandro Annibaldi; David Michod; Linda Vanetta; Steeve Cruchet; Pascal Nicod; Gilles Dubuis; Christelle Bonvin; Christian Widmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-27 |
Journal Detail:
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Title: Experimental cell research Volume: 315 ISSN: 1090-2422 ISO Abbreviation: Exp. Cell Res. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-08 Completed Date: 2009-07-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 2081-91 Citation Subset: IM |
Affiliation:
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Department of Physiology, Lausanne University, Lausanne, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs Animals Antineoplastic Agents / pharmacology Apoptosis* Cell Nucleus / metabolism* Cells, Cultured Cisplatin / pharmacology Cytoplasm / metabolism* Humans Mice ras GTPase-Activating Proteins / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/ras GTPase-Activating Proteins; 15663-27-1/Cisplatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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