---
_id: '7340'
abstract:
- lang: eng
  text: Coupling of endoplasmic reticulum stress to dimerisation‑dependent activation
    of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone
    ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal
    domain (IRE1LD) that favours the latter's monomeric inactive state and loss of
    ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations
    is presently lacking. We report that enforced loading of endogenous BiP onto endogenous
    IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that
    de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated
    BiP‑induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry
    profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent
    with active destabilisation of the IRE1LD dimer. Together, these observations
    support a competition model whereby waning ER stress passively partitions ERdj4
    and BiP to IRE1LD to initiate active repression of UPR signalling.
acknowledgement: We thank the CIMR flow cytometry core facility team (Reiner Schulte,
  Chiara Cossetti and Gabriela Grondys-Kotarba) for assistance with FACS, the Huntington
  lab for access to the Octet machine, Steffen Preissler for advice on data interpretation,
  Roman Kityk and Nicole Luebbehusen for help and advice with HX-MS experiments.
article_number: e50793
article_processing_charge: No
article_type: original
author:
- first_name: Niko Paresh
  full_name: Amin-Wetzel, Niko Paresh
  id: E95D3014-9D8C-11E9-9C80-D2F8E5697425
  last_name: Amin-Wetzel
- first_name: Lisa
  full_name: Neidhardt, Lisa
  last_name: Neidhardt
- first_name: Yahui
  full_name: Yan, Yahui
  last_name: Yan
- first_name: Matthias P.
  full_name: Mayer, Matthias P.
  last_name: Mayer
- first_name: David
  full_name: Ron, David
  last_name: Ron
citation:
  ama: Amin-Wetzel NP, Neidhardt L, Yan Y, Mayer MP, Ron D. Unstructured regions in
    IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression
    of the UPR. <i>eLife</i>. 2019;8. doi:<a href="https://doi.org/10.7554/eLife.50793">10.7554/eLife.50793</a>
  apa: Amin-Wetzel, N. P., Neidhardt, L., Yan, Y., Mayer, M. P., &#38; Ron, D. (2019).
    Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal
    domain dimer and repression of the UPR. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.50793">https://doi.org/10.7554/eLife.50793</a>
  chicago: Amin-Wetzel, Niko Paresh, Lisa Neidhardt, Yahui Yan, Matthias P. Mayer,
    and David Ron. “Unstructured Regions in IRE1α Specify BiP-Mediated Destabilisation
    of the Luminal Domain Dimer and Repression of the UPR.” <i>ELife</i>. eLife Sciences
    Publications, 2019. <a href="https://doi.org/10.7554/eLife.50793">https://doi.org/10.7554/eLife.50793</a>.
  ieee: N. P. Amin-Wetzel, L. Neidhardt, Y. Yan, M. P. Mayer, and D. Ron, “Unstructured
    regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer
    and repression of the UPR,” <i>eLife</i>, vol. 8. eLife Sciences Publications,
    2019.
  ista: Amin-Wetzel NP, Neidhardt L, Yan Y, Mayer MP, Ron D. 2019. Unstructured regions
    in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and
    repression of the UPR. eLife. 8, e50793.
  mla: Amin-Wetzel, Niko Paresh, et al. “Unstructured Regions in IRE1α Specify BiP-Mediated
    Destabilisation of the Luminal Domain Dimer and Repression of the UPR.” <i>ELife</i>,
    vol. 8, e50793, eLife Sciences Publications, 2019, doi:<a href="https://doi.org/10.7554/eLife.50793">10.7554/eLife.50793</a>.
  short: N.P. Amin-Wetzel, L. Neidhardt, Y. Yan, M.P. Mayer, D. Ron, ELife 8 (2019).
date_created: 2020-01-19T23:00:39Z
date_published: 2019-12-24T00:00:00Z
date_updated: 2026-04-03T09:44:20Z
day: '24'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.7554/eLife.50793
external_id:
  isi:
  - '000512303700001'
  pmid:
  - '31873072'
file:
- access_level: open_access
  checksum: 29fcbcd8c1fc7f11a596ed7f14ea1c82
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-19T11:37:41Z
  date_updated: 2020-11-19T11:37:41Z
  file_id: '8777'
  file_name: 2019_eLife_AminWetzel.pdf
  file_size: 4817384
  relation: main_file
  success: 1
file_date_updated: 2020-11-19T11:37:41Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal
  domain dimer and repression of the UPR
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 8
year: '2019'
...