Format

Send to:

Choose Destination
See comment in PubMed Commons below
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

  • 1Howard Hughes Medical Institute and Department of Biochemistry and Biophysics University of California, School of Medicine, San Francisco 94143-0448, USA.

Abstract

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.

PMID:
10619423
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk