Schewe and Aguirre-Ghiso (2009) demonstrated that the phosphorylation of eIF2α is an indispensable aspect of PERK-mediated apoptosis. They studied a bortezomib-resistant subpopulation of myeloma cells and found that resistance could be reversed by inhibition of the eIF2α phosphatase or by competitive inhibition of the phosphatase via overexpression of a mutant phosphorylated eIF2α. In both conditions, cells with experimentally enhanced levels of endogenous phosphorylated eIF2α regained sensitivity to bortezomib (Schewe and Aguirre-Ghiso, 2009). The gene discussed is EIF2AK3; the disease is plasma cell myeloma.