ATF4 and plasma cell myeloma: Obeng et al. (2006) have reported that Bortezomib treatment upregulates PERK activity as measured by ATF4 and downstream CHOP expression. Further, they correlated ER stress to bortezomib response by measuring the retention of immunoglobulin protein accumulating in treated cells. Myeloma cells that retained more of their secretory protein load, one hallmark of ER stress, showed more activation of ER stress markers and more sensitivity to the drug (Obeng et al., 2006).