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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis* / drug effects
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Base Sequence
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Guanosine Diphosphate / metabolism
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Humans
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Ikaros Transcription Factor
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Interleukin-2 / pharmacology
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Interleukin-2 / physiology
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Mice
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Mutation
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Phosphotyrosine / metabolism
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Proto-Oncogene Proteins p21(ras) / genetics
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Proto-Oncogene Proteins p21(ras) / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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T-Lymphocytes / cytology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors
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Transcriptional Activation* / drug effects
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Yeasts / genetics
Substances
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IKZF3 protein, human
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Ikzf3 protein, mouse
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Interleukin-2
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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Guanosine Diphosphate
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Ikaros Transcription Factor
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Phosphotyrosine
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)