2026-06-03T11:49:05Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/202122024-09-27T09:28:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Orsi, Andrea
author
van Anken, Eelco
author
Vitale, Milena
author
Zamai, Moreno
author
Caiolfa, Valeria R
author
Sitia, Roberto
author
Bakunts, Anush
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2024-07-08T14:20:23Z
2024-07-08T14:20:23Z
2024-09
Life Sci Alliance. 2024 Jun 17;7(9):e202302562.
10.26508/lsa.202302562
2575-1077
Life science alliance
38886017
http://hdl.handle.net/20.500.12105/20212
The unfolded protein response can switch from a pro-survival to a maladaptive, pro-apoptotic mode. During ER stress, IRE1α sensors dimerize, become phosphorylated, and activate XBP1 splicing, increasing folding capacity in the ER protein factory. The steps that turn on the IRE1α endonuclease activity against endogenous mRNAs during maladaptive ER stress are still unknown. Here, we show that although necessary, IRE1α dimerization is not sufficient to trigger phosphorylation. Random and/or guided collisions among IRE1α dimers are needed to elicit cross-phosphorylation and endonuclease activities. Thus, reaching a critical concentration of IRE1α dimers in the ER membrane is a key event. Formation of stable IRE1α clusters is not necessary for RNase activity. However, clustering could modulate the potency of the response, promoting interactions between dimers and decreasing the accessibility of phosphorylated IRE1α to phosphatases. The stepwise activation of IRE1α molecules and their low concentration at the steady state prevent excessive responses, unleashing full-blown IRE1 activity only upon intense stress conditions.
eng
Congress of multiple dimers is needed for cross-phosphorylation of IRE1α and its RNase activity.
journal article
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URL
https://repisalud.isciii.es/bitstreams/6ad2dcf9-f8be-4c7e-bf10-6da68422dfbe/download
File
MD5
a3b201c92c540c57fc46a826f66fb617
3031028
application/pdf
Congress of multiple dimers_Life Sci Alliance_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/ba685330-d248-49ec-ade1-6f3461853011/download
File
MD5
7d0563d6c1f6585b61022f183d4ff454
59192
text/plain
Congress of multiple dimers_Life Sci Alliance_2024.pdf.txt