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.
Romero
F
F
Laboratoire d'Oncologie Cellulaire et Moleculaire, INSERM U363, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, F-75014 Paris, France.
Martínez-A
C
C
Camonis
J
J
Rebollo
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D051740:Ikaros Transcription Factor; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D009154:Mutation; D019000:Phosphotyrosine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000187:drug effects; D015003:Yeasts / Q000235:genetics
C106285:IKZF3 protein, human; C491396:Ikzf3 protein, mouse; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D006153:Guanosine Diphosphate; D051740:Ikaros Transcription Factor; D019000:Phosphotyrosine; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)