Distinct Domains for Anti- and Pro-apoptotic Activities of IEX-1

摘要: IEX-1 (immediate early response gene X-1) is a stress-inducible gene. Its overexpression can suppress or enhance apoptosis dependent on the nature of stress, yet polypeptide does not possess any functional domains that are homologous to those present in well characterized effectors inhibitors apoptosis. This study using sequence-targeting mutagenesis reveals transmembrane-like integrated region protein be critical for both pro-apoptotic and anti-apoptotic functions. Substitution key hydrophobic residues with hydrophilic ones within this impairs capacity positively negatively regulate Mutations at N-linked glycosylation phosphorylation sites truncation C terminus also abrogated its potential promote cell survival. However, distinguished from domain, these mutants preserved activity fully. On contrary, mutation nuclear localization sequence, despite importance apoptosis, did impede IEX-1-mediated Strikingly, all lose their ability unable prevent acute increases production intracellular reactive oxygen species (ROS) initial onset whereas sustain anti-death function control ROS as sufficiently wild-type IEX-1. These findings suggest role regulation homeostasis, providing new insight into mechanism underlying