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

We searched for proteins that interact with Ras in interleukin (IL)-2-stimu lated or IL-2-deprived cells, and found that the transcription factor Aiolo s 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 fun ctional Aiolos-binding sites in the Bcl-2 promoter, which are able to activ ate the luciferase reporter gene. Mutation of Aiolos-binding sites within t he Bcl-2 promoter inhibits transactivation of the reporter gene luciferase, suggesting direct control of Bcl-2 expression by Aiolos. Co-transfection e xperiments confirm that Aiolos induces Bcl-2 expression and prevents apopto sis in IL-2-deprived cells. We propose a model for the regulation of Bcl-2 expression via Aiolos.