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

PloS One
Michela GarofaloGerolama Condorelli

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.

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Citations

May 29, 2010·Cell Death and Differentiation·C QuintavalleG Condorelli
Jun 6, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Khairunnisa' Md YusofWan Zurinah Wan Ngah
Sep 21, 2013·Cancer Investigation·Lili JiangXueshan Qiu
Jan 31, 2014·Journal of Cellular Physiology·Cristina QuintavalleGerolama Condorelli
Jun 9, 2016·Cellular Signalling·Silvia ContiElio Ziparo
Dec 14, 2018·International Journal of Molecular Sciences·Marilina García-ArandaMaximino Redondo

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Methods Mentioned

BETA
two hybrid
electrophoresis
Two-hybrid
PCR
Assay
Co-immunoprecipitation
transfection
FACS

Software Mentioned

ProQuest

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