Regulation of cell fate by the IRE1 α-TRAF2-JNK axis

Abstract

Eukaryotic cells produce proteins continuously through translation, folding and quality control within the endoplasmic reticulum (ER). When unfolded proteins accumulate in the endoplasmic reticulum the unfolded protein response (UPR) attempts to restore cellular function by reducing the load of unfolded proteins. If cellular function is not restored the unfolded protein response causes cell death through apoptosis. The only known unfolded protein response protein in lower eukaryotes is inositol-requiring enzyme 1 α (IRE1 α). In this thesis we investigated whether the kinase domain of inositol-requiring enzyme 1 α alone regulates apoptosis or whether the RNase domain is required for apoptotic cell death through the unfolded. We found evidence to suggest that inositol-requiring enzyme 1 α kinase domain alone does not cause apoptosis. Juxtaposing these results, the kinase domain alone causes the presence of phosphorylated proteins that are precursors to apoptosis. Two theories are that mutations made to deactivate the RNase domain effected the folding of the kinase domain reducing its potency. The second theory is that inositol-requiring enzyme 1 α RNase domain plays an unknown role in apoptotic cell death in the unfolded protein response.