Chunk #10 — Introduction — MiR-15/16 and DLEU7 at 13q14: a unique collaboration of coding and noncoding genes in indolent CLL — DLEU7, a second tumor suppressor at 13q14
Nuclear factor of activated T-cells (NFAT) can also be activated by TACI and BCMA, same molecules responsible for NF-kB activation (Figure 1) [25]. Previous reports showed that nuclear activated NFAT is a hallmark of unstimulated CLL cells and that NFAT is a critical factor for CD5 expression in B-cells [26, 27]. Since Dleu7 inhibits NF-kB activation by TACI and BCMA, we hypothesized that Dleu7 can also inhibit the ability of TACI and BCMA to induce NFAT mediated transactivation. Indeed, we showed that Dleu7 expression inhibited this activation ~8 fold and concluded that Dleu7 functions as NFAT inhibitor [20]. Further co-immunoprecipitation experiments confirmed that Dleu7 functions as TACI and BCMA inhibitor by direct association with these molecules [20]. Although these data strongly indicate that Dleu7 might function as a tumor suppressor in CLL it is important to show this function in cellular assays. To show that this Dleu7 can indeed function a tumor suppressor we used adenovirus expressing Dleu7 and GFP, as a control. These experiments showed that Dleu7 expression results in >2 fold decrease of cells in the S phase
