The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity.

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Version: Final published version
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Version: Author's accepted manuscript
Serval ID
serval:BIB_AE24A86BBD7D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity.
Journal
Cellular Signalling
Author(s)
Vanli G., Peltzer N., Dubuis G., Widmann C.
ISSN
1873-3913 (Electronic)
ISSN-L
0898-6568
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
26
Number
12
Pages
2992-2997
Language
english
Abstract
The caspase-3/p120 RasGAP module acts as a stress sensor that promotes pro-survival or pro-death signaling depending on the intensity and the duration of the stressful stimuli. Partial cleavage of p120 RasGAP generates a fragment, called fragment N, which protects stressed cells by activating Akt signaling. Akt family members regulate many cellular processes including proliferation, inhibition of apoptosis and metabolism. These cellular processes are regulated by three distinct Akt isoforms: Akt1, Akt2 and Akt3. However, which of these isoforms are required for fragment N mediated protection have not been defined. In this study, we investigated the individual contribution of each isoform in fragment N-mediated cell protection against Fas ligand induced cell death. To this end, DLD1 and HCT116 isogenic cell lines lacking specific Akt isoforms were used. It was found that fragment N could activate Akt1 and Akt2 but that only the former could mediate the protective activity of the RasGAP-derived fragment. Even overexpression of Akt2 or Akt3 could not rescue the inability of fragment N to protect cells lacking Akt1. These results demonstrate a strict Akt isoform requirement for the anti-apoptotic activity of fragment N.
Pubmed
Web of science
Create date
18/12/2014 17:55
Last modification date
20/08/2019 16:17
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