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Akt regulates drug-induced cell death through Bcl-w downregulation.

Authors :
Garofalo M
Quintavalle C
Zanca C
De Rienzo A
Romano G
Acunzo M
Puca L
Incoronato M
Croce CM
Condorelli G
Source :
PloS one [PLoS One] 2008; Vol. 3 (12), pp. e4070. Date of Electronic Publication: 2008 Dec 30.
Publication Year :
2008

Abstract

Akt is a serine threonine kinase with a major role in transducing survival signals and regulating proteins involved in apoptosis. To find new interactors of Akt involved in cell survival, we performed a two-hybrid screening in yeast using human full-length Akt c-DNA as bait and a murine c-DNA library as prey. Among the 80 clones obtained, two were identified as Bcl-w. Bcl-w is a member of the Bcl-2 family that is essential for the regulation of cellular survival, and that is up-regulated in different human tumors, such as gastric and colorectal carcinomas. Direct interaction of Bcl-w with Akt was confirmed by immunoprecipitation assays. Subsequently, we addressed the function of this interaction: by interfering with the activity or amount of Akt, we have demonstrated that Akt modulates the amount of Bcl-w protein. We have found that inhibition of Akt activity may promote apoptosis through the downregulation of Bcl-w protein and the consequential reduction in interaction of Bcl-w with pro-apoptotic members of the Bcl-2 family. Our data provide evidence that Bcl-w is a new member of the Akt pathway and that Akt may induce anti-apoptotic signals at least in part through the regulation of the amount and activity of Bcl-w.

Details

Language :
English
ISSN :
1932-6203
Volume :
3
Issue :
12
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
19114998
Full Text :
https://doi.org/10.1371/journal.pone.0004070