Endoplasmic Reticulum Stress Induces G2 Cell-Cycle Arrest via mRNA Translation of the p53 Isoform p53/47

p53 downstream pathways control G1 and G2 cell-cycle arrest, DNA repair, or apoptosis. However, it is still not clear how cells differentiate the cell-biological outcome of p53 activation in response to different types of stresses. The p53/47 isoform lacks the first 39 amino acids of full-length p53 including the Mdm2 binding site and the first trans-activation domain, and tetramers including p53/47 exhibit altered activity and biochemical properties. Here we show that endoplasmic reticulum stress promotes PERK-dependent induction of p53/47 mRNA translation and p53/47 homo-oligomerization. p53/47 induces 14-3-3σ and G2 arrest but does not affect G1 progression. This is contrary to p53FL, which promotes G1 arrest but has no effect on the G2. These results show a unique role for p53/47 in the p53 pathway and illustrate how a cellular stress leads to a defined cell-biological outcome through expression of a p53 isoform. [Display omitted] ► ER stress activates PERK, which promotes mRNA translation of the p53 isoform p53/47 ► ER stress promotes selective oligomerization of p53/47 ► p53/47 induces 14-3-3σ and G2 cell-cycle arrest but has no effect on the G1 ► Suppression of 14-3-3σ enhances p53/47-dependent apoptosis