A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death.
The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2483412?pdf=render |
| _version_ | 1818180500527775744 |
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| author | Perayot Pamonsinlapatham Réda Hadj-Slimane Françoise Raynaud Marc Bickle Claudine Corneloup Audrey Barthelaix Yves Lepelletier Perrine Mercier Matthieu Schapira Jérôme Samson Anne-Laure Mathieu Nicolas Hugo Olivier Moncorgé Ivan Mikaelian Sylvie Dufour Christiane Garbay Pierre Colas |
| author_facet | Perayot Pamonsinlapatham Réda Hadj-Slimane Françoise Raynaud Marc Bickle Claudine Corneloup Audrey Barthelaix Yves Lepelletier Perrine Mercier Matthieu Schapira Jérôme Samson Anne-Laure Mathieu Nicolas Hugo Olivier Moncorgé Ivan Mikaelian Sylvie Dufour Christiane Garbay Pierre Colas |
| author_sort | Perayot Pamonsinlapatham |
| collection | DOAJ |
| description | The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates. |
| first_indexed | 2024-12-11T21:20:45Z |
| format | Article |
| id | doaj.art-e97a2dabf7aa4f3a9ac24b82b69a64bb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T21:20:45Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e97a2dabf7aa4f3a9ac24b82b69a64bb2022-12-22T00:50:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0138e290210.1371/journal.pone.0002902A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death.Perayot PamonsinlapathamRéda Hadj-SlimaneFrançoise RaynaudMarc BickleClaudine CorneloupAudrey BarthelaixYves LepelletierPerrine MercierMatthieu SchapiraJérôme SamsonAnne-Laure MathieuNicolas HugoOlivier MoncorgéIvan MikaelianSylvie DufourChristiane GarbayPierre ColasThe Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates.http://europepmc.org/articles/PMC2483412?pdf=render |
| spellingShingle | Perayot Pamonsinlapatham Réda Hadj-Slimane Françoise Raynaud Marc Bickle Claudine Corneloup Audrey Barthelaix Yves Lepelletier Perrine Mercier Matthieu Schapira Jérôme Samson Anne-Laure Mathieu Nicolas Hugo Olivier Moncorgé Ivan Mikaelian Sylvie Dufour Christiane Garbay Pierre Colas A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. PLoS ONE |
| title | A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. |
| title_full | A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. |
| title_fullStr | A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. |
| title_full_unstemmed | A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. |
| title_short | A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. |
| title_sort | rasgap sh3 peptide aptamer inhibits rasgap aurora interaction and induces caspase independent tumor cell death |
| url | http://europepmc.org/articles/PMC2483412?pdf=render |
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