In the current article, we study the transcriptional response programs and cell viability of hepatocellular carcinoma cells exposed to bortezomib in combination with pharmacological compounds that perturb intracellular signaling to increase (nelfinavir, salubrinal) or decrease (ISRIB) the level of ATF4, a key transcriptional regulator of cellular stress responses. The gene discussed is ATF4; the disease is hepatocellular carcinoma.