Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death.

Détails

Ressource 1Télécharger: BIB_C5D8230CED35.P001.pdf (1293.35 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_C5D8230CED35
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death.
Périodique
Cell Death Discovery
Auteur(s)
Martin R., Desponds C., Eren R.O., Quadroni M., Thome M., Fasel N.
ISSN
2058-7716 (Electronic)
ISSN-L
2058-7716
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
2
Pages
16024
Langue
anglais
Résumé
The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex regulating key pathways in cell growth. Hyperactivation of mTORC1 is implicated in numerous cancers, thus making it a potential broad-spectrum chemotherapeutic target. Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. All treatments induced cleavage in the mTORC1 component, raptor, resulting in decreased raptor-mTOR interaction and subsequent inhibition of the mTORC1-mediated phosphorylation of downstream substrates (S6K and 4E-BP1). The cleavage was primarily mediated by caspase-6 and occurred at two sites. Mutagenesis at one of these sites, conferred resistance to cell death, indicating that raptor cleavage is important in chemotherapeutic apoptosis.

Pubmed
Création de la notice
04/05/2016 13:27
Dernière modification de la notice
03/03/2018 21:16
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