Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F19%3A00078174" target="_blank" >RIV/00209805:_____/19:00078174 - isvavai.cz</a>
Result on the web
<a href="http://embomolmed.embopress.org/cgi/pmidlookup?view=long&pmid=31040128" target="_blank" >http://embomolmed.embopress.org/cgi/pmidlookup?view=long&pmid=31040128</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/emmm.201810120" target="_blank" >10.15252/emmm.201810120</a>
Alternative languages
Result language
angličtina
Original language name
Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation
Original language description
Anterior gradient 2 (AGR2) is a dimeric protein disulfide isomerase family member involved in the regulation of protein quality control in the endoplasmic reticulum (ER). Mouse AGR2 deletion increases intestinal inflammation and promotes the development of inflammatory bowel disease (IBD). Although these biological effects are well established, the underlying molecular mechanisms of AGR2 function toward inflammation remain poorly defined. Here, using a protein-protein interaction screen to identify cellular regulators of AGR2 dimerization, we unveiled specific enhancers, including TMED2, and inhibitors of AGR2 dimerization, that control AGR2 functions. We demonstrate that modulation of AGR2 dimer formation, whether enhancing or inhibiting the process, yields pro-inflammatory phenotypes, through either autophagy-dependent processes or secretion of AGR2, respectively. We also demonstrate that in IBD and specifically in Crohn's disease, the levels of AGR2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. Our study demonstrates that AGR2 dimers act as sensors of ER homeostasis which are disrupted upon ER stress and promote the secretion of AGR2 monomers. The latter might represent systemic alarm signals for pro-inflammatory responses.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA19-02014S" target="_blank" >GA19-02014S: Identification of determinants associated with metastatic colorectal cancer in relation to Anterior gradient 2</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO molecular medicine
ISSN
1757-4676
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
6
Country of publishing house
GB - UNITED KINGDOM
Number of pages
19
Pages from-to
"pii: e10120"
UT code for WoS article
000470793600001
EID of the result in the Scopus database
2-s2.0-85065188436