Vpu caused rpr lacZ expression was clearly reduced in the context of reduced bsk task, and that of puc lacZ almost completely abolished in this same context. These results demonstrate that Vpu activates expression of both natural product libraries rpr and puc promoters via the JNK pathway and perhaps not by direct transcriptional regulation. Reduction of bsk task also completely suppressed Vpu induced down-regulation of DIAP1 and very nearly completely suppressed apoptosis. It’s remarkable that when Vpu was coexpressed with bsk IR beneath the control of dpp Gal4, the Vpu expression domain became enlarged when comparing to control cds expressing Vpu alone. This result might be explained by the concomitant reduction of the posterior displacement, basal extrusion and apoptosis of Vpu showing cells observed when bsk was down-regulated. Finally, bsk downregulation firmly suppressed the Vpu caused wing phenotype. Altogether, these results demonstrate that all the effects induced by Vpu both in adult wing and in the wing disc require the activity of bsk and therefore depend on the activity of JNK pathway. Significantly, the activation of rpr and puc lacZ resulting from Vpu term Cholangiocarcinoma wasn’t suppressed when P35 was coexpressed with Vpu. Thus, neither Vpu mediated activation of the JNK pathway, nor that of rpr expression, depends on activity. This supports the above conclusion that Vpu induced apoptosis is mediated by the activation of the JNK pathway. Our results showed that Vpu activates the JNK pathway upstream of, or through, bsk, which, in turn, induces the apoptosis cascade. To define more precisely the target whereby GW0742 317318-84-6 Vpu activates the JNK pathway, we tried the effect of the loss of function of several regulators of the JNK pathway on the Vpu induced wing phenotypes.. We first tested hemipterous which encodes a JNK kinase performing upstream of DJNK/ BSK. Down-regulation of hep suppressed the results of Vpu around the adult wing. Accordingly, Vpu caused puclacZ expression was paid off in a hep heterozygous mutant background while it was totally abolished in a hep hemizygous mutant background. Reduction of the side phenotype caused by Vpu was also obtained when two of the JNKKKs recognized to trigger the Hep Bsk stream were down-regulated, dTAK1 and the MLK/Slipper using UASdTak1 IR or UAS slpr IR constructs, respectively. We also tested intracellular proteins known to stimulate JNKKKs in reaction to various stimuli like the Tumor Necrosis Factor Receptor related factor 1, the Ste 20 linked kinase Misshapen, DTRAF2, DRac1 and the only two known Drosophila homologues of the TNF/TNFR members of the family, Eiger and Wengen, respectively,. We tested these candidates by down regulating their expression either by RNA interference or in heterozygous mutant contexts. Among these, only the RNAi construct targeting the adaptor protein DTRAF2 suppressed the Vpu induced wing phenotypes.