Akt Regulates Drug-Induced Cell Death through Bcl-w Downregulation

作者：Garofalo Michela^*; Quintavalle Cristina; Zanca Ciro; De Rienzo Assunta; Romano Giulia; Acunzo Mario; Puca Loredana; Incoronato Mariarosaria; Croce Carlo M; Condorelli Gerolama

来源：PLos One, 2008, 3(12): e4070.

DOI：10.1371/journal.pone.0004070

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 proapoptotic 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.

• 出版日期2008-12-30