Role of mTOR, Bad, and Survivin in RasGAP Fragment N-Mediated Cell Protection.

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State: Public
Version: Final published version
Serval ID
serval:BIB_7226E2610ED5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of mTOR, Bad, and Survivin in RasGAP Fragment N-Mediated Cell Protection.
Journal
Plos One
Author(s)
Peltzer N., Vanli G., Yang J.Y., Widmann C.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2013
Volume
8
Number
6
Pages
e68123
Language
english
Notes
Publication types: JOURNAL ARTICLE Publication Status: epublish
Abstract
Partial cleavage of p120 RasGAP by caspase-3 in stressed cells generates an N-terminal fragment, called fragment N, which activates an anti-apoptotic Akt-dependent survival response. Akt regulates several effectors but which of these mediate fragment N-dependent cell protection has not been defined yet. Here we have investigated the role of mTORC1, Bad, and survivin in the capacity of fragment N to protect cells from apoptosis. Neither rapamycin, an inhibitor of mTORC1, nor silencing of raptor, a subunit of the mTORC1 complex, altered the ability of fragment N from inhibiting cisplatin- and Fas ligand-induced death. Cells lacking Bad, despite displaying a stronger resistance to apoptosis, were still protected by fragment N against cisplatin-induced death. Fragment N was also able to protect cells from Fas ligand-induced death in conditions where Bad plays no role in apoptosis regulation. Fragment N expression in cells did neither modulate survivin mRNA nor its protein expression. Moreover, the expression of cytoplasmic survivin, known to exert anti-apoptotic actions in cells, still occurred in UV-B-irradiated epidermis of mouse expressing a caspase-3-resistant RasGAP mutant that cannot produce fragment N. Additionally, survivin function in cell cycle progression was not affected by fragment N. These results indicate that, taken individually, mTOR, Bad, or Survivin are not required for fragment N to protect cells from cell death. We conclude that downstream targets of Akt other than mTORC1, Bad, or survivin mediate fragment N-induced protection or that several Akt effectors can compensate for each other to induce the pro-survival fragment N-dependent response.
Pubmed
Web of science
Open Access
Yes
Create date
22/08/2013 16:31
Last modification date
20/08/2019 14:30
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