Expression of immediate early gene pip92 during anisomycin-induced cell death is mediated by the JNK- and p38-dependent activation of Elk1

We report here that immediate early gene pip92 is expressed during anisomyc in-induced cell death in fibroblast NIH3T3 cells. To determine the mechanis m by which this occurs and to identify downstream signaling pathways, we in vestigated the induction of the pip92 promoter. The activation of pip92 by anisomycin is mediated by the activation of MAP kinases, such as JNK and p3 8 kinase, but not ERK. Deletion analysis of the pip92 promoter indicated th at pip92 activation occurs primarily within the region containing a serum r esponse element (SRE). Further analysis of the SRE using a heterologous thy midine kinase promoter showed that both an Ets and CArG-like site are requi red for anisomycin-induced pip92 expression. Elk1, which binds to the Ets s ite, was phosphorylated by the JNK- and p38-dependent pathways and the phos phorylation of Elk1-GAL4 fusion proteins by these pathways was sufficient f or the transactivation. Overall, this study suggested that different MAPK p athways are involved in the expression of immediate early gene pip92 by gro wth factors and environmental stresses.