The resulting oligomerization of Ire1 leads to activation of its cytoplasmic kinase and endoribonuclease domain. The main function of the kinase appears to be activation of the nuclease, which requires binding of ATP or ADP in the active site of the kinase (Papa et al., 2003) . The nuclease in turn cleaves two specific sites in the mRNA encoding XBP-1 (X-box-binding protein 1), a conserved UPR transcription factor, which leads to XBP-1 activation and translation through removal of a regulatory intron.