FIG. 4.

Ire1 signaling pathway. Ire1 exists as a BiP-bound monomer in the absence of ER stress. When unfolded proteins accumulate, BiP is released, and Ire1 forms homodimers that autophosphorylate and activate an endonuclease activity encoded in its C-terminus. Activated Ire1 removes 26 bases from the XBP1 transcript, which is relegated and now encodes a fully active transcription factor, XBP1(S). XBP1(S) transactivates a number of UPR targets and, later in the response, is negatively regulated via heterodimerization with the unspliced form of XBP1 [XBP1(U)]. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article at www.liebertonline.com/ars).