Abstract
A hallmark of cellular stress response pathways is to protect cells from different environmental insults. While much is known about how cells are protected against acute stresses of different types, the mechanisms underpinning how cells are protected against gradually changing stresses are poorly understood. Here we demonstrate that a linear stress gradient but not a step, pulse or a quadratic gradient of the same stressor and intensity causes a severe cell growth phenotype. We determined that this phenotype is caused by the failure of cells to activate the stress-activated protein kinase signaling pathway due to a threshold in the rate of stress application. This lack of response occurs despite cells physically detecting the relatively slow changes in stress signal. These findings have fundamental implications for understanding mechanisms of how temporally changing environments impact biological phenotype.