Strong and sustained activation of the anticipatory unfolded protein response induces necrotic cell death.

ABSTRACT: The endoplasmic reticulum stress sensor, the unfolded protein response (UPR), regulates intracellular protein homeostasis. While transient activation of the reactive UPR by unfolded protein is protective, prolonged and sustained activation of the reactive UPR triggers CHOP-mediated apoptosis. In the recently characterized, evolutionarily conserved anticipatory UPR, mitogenic hormones and other effectors pre-activate the UPR; how strong and sustained activation of the anticipatory UPR induces cell death was unknown. To characterize this cell death pathway, we used BHPI, a small molecule that activates the anticipatory UPR through estrogen receptor α (ERα) and induces death of ERα⁺ cancer cells. We show that sustained activation of the anticipatory UPR by BHPI kills cells by induc

SUBMITTER: Livezey M 

PROVIDER: S-EPMC6180055 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature