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-x(L). We show that IL-4 deprivation induces apoptosis, but does not modulate Bcl-x(L) expression. Because Bcl-x(L) does not promote cell survival in the absence of IL-4, we investigate the mechanism by which Bcl-x(L) was unable to inhibit apoptosis. Using yeast two-hybrid system, coimmunoprecipitation, and indirect immunofluorescence techniques, we found that Bcl-x(L) 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-x(L), but induces tyrosine phosphorylation of Aiolos, which is required for dissociation from Bcl-x(L). Transfection experiments confirm that cells overexpressing Bcl-x(L) are able to prevent apoptosis in the absence of IL-4. On the contrary, cells that overexpress Bcl-x(L) and Aiolos are unable to block apoptosis in the absence of IL-4. We propose a model for the regulation of the Bcl-x(L) anti-apoptotic role via Aiolos.