Bibliographic Details
| Title: |
A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death. |
| Authors: |
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 |
| Source: |
PLoS ONE, Vol 3, Iss 8, p e2902 (2008) |
| Publisher Information: |
Public Library of Science (PLoS), 2008. |
| Publication Year: |
2008 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
http://europepmc.org/articles/PMC2483412?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0002902 |
| Access URL: |
https://doaj.org/article/e97a2dabf7aa4f3a9ac24b82b69a64bb |
| Accession Number: |
edsdoj.97a2dabf7aa4f3a9ac24b82b69a64bb |
| Database: |
Directory of Open Access Journals |
