Send to

Choose Destination
Cell. 1999 Dec 23;99(7):691-702.

A role for presenilin-1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response.

Author information

Howard Hughes Medical Institute and Department of Biochemistry and Biophysics University of California, School of Medicine, San Francisco 94143-0448, USA.


The unfolded protein response (UPR) mediates signaling from the endoplasmic reticulum to the nucleus. In yeast, a key regulatory step in the UPR is the spliceosome-independent splicing of HAC1 mRNA encoding a UPR-specific transcription factor, which is initiated by the transmembrane kinase/endoribonuclease Ire1. We show that yeast HAC1 mRNA is correctly spliced in mammalian cells upon UPR induction and that mammalian Ire1 can precisely cleave both splice junctions. Surprisingly, UPR induction leads to proteolytic cleavage of Ire1, releasing fragments containing the kinase and nuclease domains that accumulate in the nucleus. Nuclear localization and UPR induction are reduced in presenilin-1 knockout cells. These results suggest that the salient features of the UPR are conserved among eukaryotic cells and that presenilin-1 controls Ire1 proteolysis in mammalian cells.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center