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-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.
Mesh Terms:
Animals, Apoptosis, Base Sequence, Cell Line, Cell Nucleus, Cytoplasm, Guanosine Diphosphate, Humans, Ikaros Transcription Factor, Interleukin-2, Mice, Mutation, Phosphotyrosine, Promoter Regions, Genetic, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins p21(ras), RNA, Messenger, Recombinant Fusion Proteins, T-Lymphocytes, Trans-Activators, Transcription Factors, Transcriptional Activation, Yeasts
Animals, Apoptosis, Base Sequence, Cell Line, Cell Nucleus, Cytoplasm, Guanosine Diphosphate, Humans, Ikaros Transcription Factor, Interleukin-2, Mice, Mutation, Phosphotyrosine, Promoter Regions, Genetic, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins p21(ras), RNA, Messenger, Recombinant Fusion Proteins, T-Lymphocytes, Trans-Activators, Transcription Factors, Transcriptional Activation, Yeasts
EMBO J.
Date: Jun. 15, 1999
PubMed ID: 10369681
View in: Pubmed Google Scholar
Download Curated Data For This Publication
7845
Switch View:
- Interactions 4