Highlights • IRE1α forms an ER-stress-independent complex with the Sec61/Sec63 translocon • IRE1α binding to BiP chaperone relies on its association with Sec61/Sec63 • Sec63 attenuates IRE1α signaling by mediating BiP binding to IRE1α during ER stress • IRE1α remains activated in Sec63-deficient cells during prolonged ER stress Summary Misfolded proteins in the endoplasmic reticulum (ER) activate IRE1α endoribonuclease in mammalian cells, which mediates XBP1 mRNA splicing to produce an active...
