Revisiting G3BP1 as a RasGAP Binding Protein: Sensitization of Tumor Cells to Chemotherapy by the RasGAP 317–326 Sequence Does Not Involve G3BP1
| Autor: | Jamal Tazi, Sophie G. Martin, Christian Widmann, Aline Dousse, Alessandro Annibaldi |
|---|---|
| Přispěvatelé: | Laboratoire de Spectrométrie Ionique et Moléculaire (LASIM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2011 |
| Předmět: |
Proteomics
Untranslated region Cancer Treatment Apoptosis Plasma protein binding Biochemistry Mice 0302 clinical medicine Cricetinae Molecular Cell Biology Signaling in Cellular Processes Poly-ADP-Ribose Binding Proteins Peptide sequence Apoptotic Signaling Cascade Apoptotic Signaling 0303 health sciences Multidisciplinary Cell Death Signaling Cascades Cell biology RNA Recognition Motif Proteins Oncology ras GTPase-Activating Proteins 030220 oncology & carcinogenesis Medicine RNA Helicases Protein Binding Research Article Signal Transduction Immunoprecipitation Science Ras Signaling Biology 03 medical and health sciences Stress granule Tumor Cricetinae Drug Resistance Cell Line Tumor Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence Protein Interactions 030304 developmental biology Messenger RNA Binding protein DNA Helicases Neoplasm/drug effects Humans Mice Mutagens/pharmacology Peptide Fragments/chemistry/*pharmacology Protein Binding ras GTPase-Activating Proteins/*chemistry/*metabolism Proteins Chemotherapy and Drug Treatment Amino Acid Sequence Animals Apoptosis/drug effects Carrier Proteins/*metabolism Cell Line Molecular biology Peptide Fragments Drug Resistance Neoplasm Carrier Proteins Mutagens |
| Zdroj: | PLoS ONE, Vol 6, Iss 12, p e29024 (2011) PLoS One, vol. 6, no. 12, pp. e29024 PloS one PLoS ONE PLoS ONE, Public Library of Science, 2011, 6 (12), pp.e29024. ⟨10.1371/journal.pone.0029024⟩ |
| ISSN: | 1932-6203 |
| Popis: | International audience; RasGAP is a multifunctional protein that controls Ras activity and that is found in chromosomal passenger complexes. It also negatively or positively regulates apoptosis depending on the extent of its cleavage by caspase-3. RasGAP has been reported to bind to G3BP1 (RasGAP SH3-domain-binding protein 1), a protein regulating mRNA stability and stress granule formation. The region of RasGAP (amino acids 317-326) thought to bind to G3BP1 corresponds exactly to the sequence within fragment N2, a caspase-3-generated fragment of RasGAP, that mediates sensitization of tumor cells to genotoxins. While assessing the contribution of G3BP1 in the anti-cancer function of a cell-permeable peptide containing the 317-326 sequence of RasGAP (TAT-RasGAP(3)(1)(7)(-)(3)(2)(6)), we found that, in conditions where G3BP1 and RasGAP bind to known partners, no interaction between G3BP1 and RasGAP could be detected. TAT-RasGAP(3)(1)(7)(-)(3)(2)(6) did not modulate binding of G3BP1 to USP10, stress granule formation or c-myc mRNA levels. Finally, TAT-RasGAP(3)(1)(7)(-)(3)(2)(6) was able to sensitize G3BP1 knock-out cells to cisplatin-induced apoptosis. Collectively these results indicate that G3BP1 and its putative RasGAP binding region have no functional influence on each other. Importantly, our data provide arguments against G3BP1 being a genuine RasGAP-binding partner. Hence, G3BP1-mediated signaling may not involve RasGAP. |
| Databáze: | OpenAIRE |
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