Akt regulates drug-induced cell death through Bcl-w downregulation.
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.
Garofalo
Michela
M
Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, Naples, Italy.
Quintavalle
Cristina
C
Zanca
Ciro
C
De Rienzo
Assunta
A
Romano
Giulia
G
Acunzo
Mario
M
Puca
Loredana
L
Incoronato
Mariarosaria
M
Croce
Carlo M
CM
Condorelli
Gerolama
G
D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D051057:Proto-Oncogene Proteins c-akt