The association of Aiolos transcription factor and Bcl-xL is involved in the control of apoptosis.
We have analyzed the mechanism implicated in the control of the anti-apoptotic role of Bcl-xL. We show that IL-4 deprivation induces apoptosis, but does not modulate Bcl-xL expression. Because Bcl-xL does not promote cell survival in the absence of IL-4, we investigate the mechanism by which Bcl-xL was unable to inhibit apoptosis. Using yeast two-hybrid system, coimmunoprecipitation, and indirect immunofluorescence techniques, we found that Bcl-xL interacts with the transcription factor Aiolos in IL-4-stimulated cells, increasing upon IL-4 deprivation. IL-4 does not promote translocation of Aiolos or Bcl-xL, but induces tyrosine phosphorylation of Aiolos, which is required for dissociation from Bcl-xL. Transfection experiments confirm that cells overexpressing Bcl-xL are able to prevent apoptosis in the absence of IL-4. On the contrary, cells that overexpress Bcl-xL and Aiolos are unable to block apoptosis in the absence of IL-4. We propose a model for the regulation of the Bcl-xL anti-apoptotic role via Aiolos.
Rebollo
A
A
Centro Nacional de Biotecnología, Department of Immunology and Oncology, Campus de Cantoblanco, Universidad Autónoma de Madrid, Madrid, Spain. arebollo@cnb.uam.es
Ayllón
V
V
Fleischer
A
A
Martínez
C A
CA
Zaballos
A
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D017077:Culture Media, Conditioned / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D017077:Culture Media, Conditioned; C106285:IKZF3 protein, human; C491396:Ikzf3 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D014157:Transcription Factors; D051020:bcl-X Protein; D051740:Ikaros Transcription Factor; D015847:Interleukin-4; D014443:Tyrosine