P53-mediated suppression of BiP triggers BIK-induced apoptosis during prolonged endoplasmic reticulum stress.

ABSTRACT: Physiological and pathological conditions that affect the folding capacity of the endoplasmic reticulum (ER) provoke ER stress and trigger the unfolded protein response (UPR). The UPR aims to either restore the balance between newly synthesized and misfolded proteins or if the damage is severe, to trigger cell death. However, the molecular events underlying the switch between repair and cell death are not well understood. The ER-resident chaperone BiP governs the UPR by sensing misfolded proteins and thereby releasing and activating the three mediators of the UPR: PERK, IRE1 and ATF6. PERK promotes G2 cell cycle arrest and cellular repair by inducing the alternative translated p53 isoform p53ΔN40 (p53/47), which activates 14-3-3σ via suppression of p21^CDKN1A. Here we show that p

SUBMITTER: Lopez I 

PROVIDER: S-EPMC5596431 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature