BAX is activated in response to numerous proapoptotic stimuli and mediates apoptosis through the intrinsic pathway. We identified just one putative KLF5 binding site from Lapatinib clinical trial 449 to 437 upstream of the translation start site and, by ChIP assay, demonstrated KLF5 binding to ASK1 in the vicinity of this putative binding site. The ASK1 target MKK4 was also increased at the mRNA and protein levels following KLF5 induction. But, no significant increase in MKK7 was seen upon induction, indicating the nature for MKK4. Surprisingly, by ChIP, KLF5 bound to the 5 regulatory region of MKK4 in a area from 126 to 72 expected to have six KLF5 binding sites. At the protein level, KLF5 induction increased both complete MKK4 and MKK4 phosphorylation, the former likely by direct transactivation of MKK4 and the latter through ASK1 up-regulation. Consistent with this, treatment of cells with PD98059, a small molecule inhibitor of MKK4 phosphorylation, blocked MKK4 phosphorylation but didn’t affect Plastid overall MKK4. The development and progression of cancers, including ESCC, demand several essential steps including alteration in the get a handle on of cell proliferation, survival, metastasis, and evasion of apoptosis. Recently, we identified KLF5 reduction as a vital step in the development of determined and ESCC KLF5, through the cyclin dependent kinase inhibitor p21Waf1/Cip1, as an important brake on an aberrant cell cycle. The functions of KLF5 in these procedures are generally mediated by direct transcriptional regulation of its target genes, and KLF5 might have equally transactivating and repressive functions. Here, we define a novel and essential function for KLF5 within the activation of JNK signaling to control apoptosis and ESCC cell viability. Of note, we have previously examined the results of KLF5 on apoptosis in ESCC cells and found similar implications, and subtle differences here might be due to inducible instead of constitutive KLF5 phrase. Transcriptional control of multiple methods in the JNK pathway by KLF5 is characteristic of a coherent feed forward loop and is indicative of the crucial Cediranib structure role of KLF5 in the regulation of this signaling network. When KLF5 is induced in ESCC cells, JNK inhibition significantly sustains but does not completely relief cell viability. These data suggest that, while JNK signaling is the major mediator of cell viability and apoptosis induced by KLF5 in ESCC cells, KLF5 transcriptional regulation of BAX and probably other genes might be functionally relevant. The truth is, we discover that quite a few other apoptotic and success facets will also be altered by induction in ESCC cells. Moreover, ASK1 and MKK4 can also trigger p38 MAPK, and PD98059 can also inhibit other MAP2Ks. Therefore, future studies will be directed toward understanding the role of KLF5 in the service of other MAPK pathways in ESCC and in the transcriptional regulation of other proapoptotic and anti-apoptotic factors.