Revisiting G3BP1 as a RasGAP binding protein: sensitization of tumor cells to chemotherapy by the RasGAP 317-326 sequence does not involve G3BP1.

Abstract

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-RasGAP₃₁₇₋₃₂₆), we found that, in conditions where G3BP1 and RasGAP bind to known partners, no interaction between G3BP1 and RasGAP could be detected. TAT-RasGAP₃₁₇₋₃₂₆ did not modulate binding of G3BP1 to USP10, stress granule formation or c-myc mRNA levels. Finally, TAT-RasGAP₃₁₇₋₃₂₆ 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.

• Authors: Alessandro Annibaldi, Aline Dousse, Sophie Martin, Jamal Tazi, Christian Widmann
• Journal: PloS one (PLoS One) Vol. 6 Issue 12 Pg. e29024 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22205990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Mutagens
• Peptide Fragments
• Poly-ADP-Ribose Binding Proteins
• RNA Recognition Motif Proteins
• ras GTPase-Activating Proteins
• DNA Helicases
• G3bp1 protein, mouse
• RNA Helicases

Topics

• Amino Acid Sequence
• Animals
• Apoptosis (drug effects)
• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Cricetinae
• DNA Helicases
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Mice
• Mutagens (pharmacology)
• Peptide Fragments (chemistry, pharmacology)
• Poly-ADP-Ribose Binding Proteins
• Protein Binding
• RNA Helicases
• RNA Recognition Motif Proteins
• ras GTPase-Activating Proteins (chemistry, metabolism)