The regulatory effects of low-dose ionizing radiation on Ikaros-autotaxin interaction

Ikaros, a transcription factor containing zinc-finger motif, has known as a critical regulator of hematopoiesis in immune system. Ikaros protein modulates the transcription of target genes via binding to the regulatory elements of the genes promoters. However the regulatory function of Ikaros in other organelle except nuclear remains to be determined. This study explored radiation-induced modulatory function of Ikaros in cytoplasm. The results showed that Ikaros protein lost its DNA binding ability after LDIR (low-dose ionizing radiation) exposure. Cell fractionation and Western blot analysis showed that Ikaros protein was translocated into cytoplasm from nuclear by LDIR. This was confirmed by immunofluorescence assay. We identified Autotaxin as a novel protein which potentially interacts with Ikaros through in vitro protein-binding screening. Co-immunoprecipitation assay revealed that Ikaros and Autotaxin are able to bind each other. Autotaxin is a crucial enzyme generating lysophosphatidic acid (LPA), a phospholipid mediator, which has potential regulatory effects on immune cell growth and motility. Our results indicate that LDIR potentially regulates immune system via protein-protein interaction of Ikaros and Autotaxin