Aiolos transcription factor controls cell death in Tcells by regulating Bcl-2 expression and its cellular localization

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Abstract
We searched for proteins that interact with Ras in interleukin (IL)‐2‐stimulated or IL‐2‐deprived cells, and found that the transcription factor Aiolos interacts with Ras. The Ras–Aiolos interaction was confirmed in vitro and in vivo by co‐immunoprecipitation. Indirect immunofluorescence shows that IL‐2 controls the cellular distribution of Aiolos and induces its tyrosine phosphorylation, required for dissociation from Ras. We also identified functional Aiolos‐binding sites in the Bcl‐2 promoter, which are able to activate the luciferase reporter gene. Mutation of Aiolos‐binding sites within the Bcl‐2 promoter inhibits transactivation of the reporter gene luciferase, suggesting direct control of Bcl‐2 expression by Aiolos. Co‐transfection experiments confirm that Aiolos induces Bcl‐2 expression and prevents apoptosis in IL‐2‐deprived cells. We propose a model for the regulation of Bcl‐2 expression via Aiolos.