A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317-326 Peptide.

Détails

Ressource 1Télécharger: J. Biol. Chem.-2014-Barras-23701-11.pdf (2289.52 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_D389856AB093
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317-326 Peptide.
Périodique
Journal of Biological Chemistry
Auteur(s)
Barras D., Chevalier N., Zoete V., Dempsey R., Lapouge K., Olayioye M.A., Michielin O., Widmann C.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2014
Volume
289
Numéro
34
Pages
23701-23711
Langue
anglais
Résumé
TAT-RasGAP317-326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317-326 sequence for the anticancer activities of TAT-RasGAP317-326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317-326.
Mots-clé
Cell Migration, Cell-penetrating peptide (CPP), Deleted in Liver Cancer 1 (DLC1), Docking, GTPase-activating Protein (GAP), Peptides, RasGAP, TAT-RasGAP(317-326), Anticancer Peptide, Sensitizer
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/10/2014 17:30
Dernière modification de la notice
20/08/2019 15:53
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