DDIT3 was identified as a C/EBP-homologous protein that inhibits C/EBP and LAP in a dominant-negative manner (1). DDIT3 expression is induced by certain cellular stresses including starvation and the induced DDIT3 suppresses cell cycle progression from G1 to S phase (2). Later it was shown that, during ER stress, the level of DDIT3 expression is elevated and DDIT3 functions to mediate programmed cell death (3). Studies also found that DDIT3 mediates the activation of GADD34 and Ero1-Lα expression during ER stress. GADD34 in turn dephosphorylates phospho-Ser51 of eIF2α thereby stimulating protein synthesis. Ero1-Lα promotes oxidative stress inside the endoplasmic reticulum (ER) (4). The role of DDIT3 in the programmed cell death of ER-stressed cells is correlated with its role promoting protein synthesis and oxidative stress inside the ER (4).
