Cellular stress leads to an upregulation of gene transcription. We asked if 
there is a specificity in the activation of the stress-responsive transcription 
factors Nrf2, ATF4, and AP-1/c-Jun, or if activation of these proteins is a 
redundant cellular answer toward extracellular stressors. Here, we show that 
oxidative stress, induced by stimulation of the cells with the oxidant arsenite, 
strongly activated gene transcription via the stress-responsive element (StRE), 
while phorbol ester or tunicamycin, activators of AP-1/c-Jun or ATF4, 
respectively, activated AP-1 or nutrient-sensing response element-mediated 
transcription. Preincubation of the cells with N-acetyl-cysteine or 
overexpression of thioredoxin selectively attenuated arsenite-induced 
upregulation of StRE-regulated transcription. Expression of either 
dominant-negative or constitutively active mutants of Nrf2, ATF4, or c-Jun 
confirmed that distinct transcription units are regulated by these transcription 
factors. Physiological stimuli involving the activation of either Gαq-coupled 
designer receptors or the protein kinases c-Jun N-terminal protein kinase or p38 
strongly stimulated transcription via AP-1/c-Jun, with minimal effects on Nrf2 
or ATF4-responsive promoters. Thus, activation of transcription by extracellular 
signaling molecules shows specificity at the level of the chemical nature of the 
signaling molecule, at the level of the intracellular transduction process, and 
at the level of signal-responsive transcription factors. J. Cell. Biochem. 118: 
127-140, 2017. © 2016 Wiley Periodicals, Inc.