Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation
Identifieur interne : 000575 ( Ncbi/Checkpoint ); précédent : 000574; suivant : 000576Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation
Auteurs : Marion Maurel ; Joanna Obacz ; Tony Avril ; Yong-Ping Ding ; Olga Papadodima ; Xavier Treton ; Fanny Daniel ; Eleftherios Pilalis ; Johanna Hörberg ; Wenyang Hou ; Marie-Claude Beauchamp ; Julien Tourneur-Marsille ; Dominique Cazals-Hatem ; Lucia Sommerova ; Afshin Samali ; Jan Tavernier ; Roman Hrstka ; Aurélien Dupont ; Delphine Fessart ; Frédéric Delom ; Martin E. Fernandez-Zapico ; Gregor Jansen ; Leif A. Eriksson ; David Y. Thomas ; Loydie Jerome-Majewska ; Ted Hupp ; Aristotelis Chatziioannou ; Eric Chevet ; Eric Ogier-DenisSource :
- EMBO Molecular Medicine [ 1757-4676 ] ; 2019.
Abstract
Anterior gradient 2 (
Url:
DOI: 10.15252/emmm.201810120
PubMed: 31040128
PubMed Central: 6554669
Affiliations:
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PMC:6554669Le document en format XML
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adient 2 (<styled-content style="fixed-case">AGR</styled-content>
2) dimerization links endoplasmic reticulum proteostasis to inflammation</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Control of anterior <styled-content style="fixed-case">GR</styled-content>
adient 2 (<styled-content style="fixed-case">AGR</styled-content>
2) dimerization links endoplasmic reticulum proteostasis to inflammation</title>
<author><name sortKey="Maurel, Marion" sort="Maurel, Marion" uniqKey="Maurel M" first="Marion" last="Maurel">Marion Maurel</name>
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<author><name sortKey="Obacz, Joanna" sort="Obacz, Joanna" uniqKey="Obacz J" first="Joanna" last="Obacz">Joanna Obacz</name>
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<author><name sortKey="Avril, Tony" sort="Avril, Tony" uniqKey="Avril T" first="Tony" last="Avril">Tony Avril</name>
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<author><name sortKey="Ding, Yong Ing" sort="Ding, Yong Ing" uniqKey="Ding Y" first="Yong-Ping" last="Ding">Yong-Ping Ding</name>
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<author><name sortKey="Papadodima, Olga" sort="Papadodima, Olga" uniqKey="Papadodima O" first="Olga" last="Papadodima">Olga Papadodima</name>
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<author><name sortKey="Treton, Xavier" sort="Treton, Xavier" uniqKey="Treton X" first="Xavier" last="Treton">Xavier Treton</name>
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<author><name sortKey="Pilalis, Eleftherios" sort="Pilalis, Eleftherios" uniqKey="Pilalis E" first="Eleftherios" last="Pilalis">Eleftherios Pilalis</name>
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<author><name sortKey="Horberg, Johanna" sort="Horberg, Johanna" uniqKey="Horberg J" first="Johanna" last="Hörberg">Johanna Hörberg</name>
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</affiliation>
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<author><name sortKey="Hou, Wenyang" sort="Hou, Wenyang" uniqKey="Hou W" first="Wenyang" last="Hou">Wenyang Hou</name>
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<author><name sortKey="Beauchamp, Marie Laude" sort="Beauchamp, Marie Laude" uniqKey="Beauchamp M" first="Marie-Claude" last="Beauchamp">Marie-Claude Beauchamp</name>
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<author><name sortKey="Tourneur Arsille, Julien" sort="Tourneur Arsille, Julien" uniqKey="Tourneur Arsille J" first="Julien" last="Tourneur-Marsille">Julien Tourneur-Marsille</name>
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<author><name sortKey="Cazals Atem, Dominique" sort="Cazals Atem, Dominique" uniqKey="Cazals Atem D" first="Dominique" last="Cazals-Hatem">Dominique Cazals-Hatem</name>
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<author><name sortKey="Sommerova, Lucia" sort="Sommerova, Lucia" uniqKey="Sommerova L" first="Lucia" last="Sommerova">Lucia Sommerova</name>
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<author><name sortKey="Samali, Afshin" sort="Samali, Afshin" uniqKey="Samali A" first="Afshin" last="Samali">Afshin Samali</name>
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<author><name sortKey="Hrstka, Roman" sort="Hrstka, Roman" uniqKey="Hrstka R" first="Roman" last="Hrstka">Roman Hrstka</name>
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</affiliation>
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<author><name sortKey="Dupont, Aurelien" sort="Dupont, Aurelien" uniqKey="Dupont A" first="Aurélien" last="Dupont">Aurélien Dupont</name>
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<author><name sortKey="Fessart, Delphine" sort="Fessart, Delphine" uniqKey="Fessart D" first="Delphine" last="Fessart">Delphine Fessart</name>
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<author><name sortKey="Delom, Frederic" sort="Delom, Frederic" uniqKey="Delom F" first="Frédéric" last="Delom">Frédéric Delom</name>
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</affiliation>
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<author><name sortKey="Fernandez Apico, Martin E" sort="Fernandez Apico, Martin E" uniqKey="Fernandez Apico M" first="Martin E" last="Fernandez-Zapico">Martin E. Fernandez-Zapico</name>
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</affiliation>
</author>
<author><name sortKey="Jansen, Gregor" sort="Jansen, Gregor" uniqKey="Jansen G" first="Gregor" last="Jansen">Gregor Jansen</name>
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</affiliation>
</author>
<author><name sortKey="Eriksson, Leif A" sort="Eriksson, Leif A" uniqKey="Eriksson L" first="Leif A" last="Eriksson">Leif A. Eriksson</name>
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<author><name sortKey="Thomas, David Y" sort="Thomas, David Y" uniqKey="Thomas D" first="David Y" last="Thomas">David Y. Thomas</name>
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</affiliation>
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<author><name sortKey="Jerome Ajewska, Loydie" sort="Jerome Ajewska, Loydie" uniqKey="Jerome Ajewska L" first="Loydie" last="Jerome-Majewska">Loydie Jerome-Majewska</name>
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</affiliation>
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<author><name sortKey="Chatziioannou, Aristotelis" sort="Chatziioannou, Aristotelis" uniqKey="Chatziioannou A" first="Aristotelis" last="Chatziioannou">Aristotelis Chatziioannou</name>
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<author><name sortKey="Chevet, Eric" sort="Chevet, Eric" uniqKey="Chevet E" first="Eric" last="Chevet">Eric Chevet</name>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Anterior gradient 2 (<styled-content style="fixed-case">AGR</styled-content>
2) is a dimeric protein disulfide isomerase family member involved in the regulation of protein quality control in the endoplasmic reticulum (<styled-content style="fixed-case">ER</styled-content>
). Mouse <styled-content style="fixed-case">AGR</styled-content>
2 deletion increases intestinal inflammation and promotes the development of inflammatory bowel disease (<styled-content style="fixed-case">IBD</styled-content>
). Although these biological effects are well established, the underlying molecular mechanisms of <styled-content style="fixed-case">AGR</styled-content>
2 function toward inflammation remain poorly defined. Here, using a protein–protein interaction screen to identify cellular regulators of <styled-content style="fixed-case">AGR</styled-content>
2 dimerization, we unveiled specific enhancers, including <styled-content style="fixed-case">TMED</styled-content>
2, and inhibitors of <styled-content style="fixed-case">AGR</styled-content>
2 dimerization, that control <styled-content style="fixed-case">AGR</styled-content>
2 functions. We demonstrate that modulation of <styled-content style="fixed-case">AGR</styled-content>
2 dimer formation, whether enhancing or inhibiting the process, yields pro‐inflammatory phenotypes, through either autophagy‐dependent processes or secretion of <styled-content style="fixed-case">AGR</styled-content>
2, respectively. We also demonstrate that in <styled-content style="fixed-case">IBD</styled-content>
and specifically in Crohn's disease, the levels of <styled-content style="fixed-case">AGR</styled-content>
2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. Our study demonstrates that <styled-content style="fixed-case">AGR</styled-content>
2 dimers act as sensors of <styled-content style="fixed-case">ER</styled-content>
homeostasis which are disrupted upon <styled-content style="fixed-case">ER</styled-content>
stress and promote the secretion of <styled-content style="fixed-case">AGR</styled-content>
2 monomers. The latter might represent systemic alarm signals for pro‐inflammatory responses.</p>
</div>
</front>
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<tree><noCountry><name sortKey="Avril, Tony" sort="Avril, Tony" uniqKey="Avril T" first="Tony" last="Avril">Tony Avril</name>
<name sortKey="Beauchamp, Marie Laude" sort="Beauchamp, Marie Laude" uniqKey="Beauchamp M" first="Marie-Claude" last="Beauchamp">Marie-Claude Beauchamp</name>
<name sortKey="Cazals Atem, Dominique" sort="Cazals Atem, Dominique" uniqKey="Cazals Atem D" first="Dominique" last="Cazals-Hatem">Dominique Cazals-Hatem</name>
<name sortKey="Chatziioannou, Aristotelis" sort="Chatziioannou, Aristotelis" uniqKey="Chatziioannou A" first="Aristotelis" last="Chatziioannou">Aristotelis Chatziioannou</name>
<name sortKey="Chevet, Eric" sort="Chevet, Eric" uniqKey="Chevet E" first="Eric" last="Chevet">Eric Chevet</name>
<name sortKey="Daniel, Fanny" sort="Daniel, Fanny" uniqKey="Daniel F" first="Fanny" last="Daniel">Fanny Daniel</name>
<name sortKey="Delom, Frederic" sort="Delom, Frederic" uniqKey="Delom F" first="Frédéric" last="Delom">Frédéric Delom</name>
<name sortKey="Ding, Yong Ing" sort="Ding, Yong Ing" uniqKey="Ding Y" first="Yong-Ping" last="Ding">Yong-Ping Ding</name>
<name sortKey="Dupont, Aurelien" sort="Dupont, Aurelien" uniqKey="Dupont A" first="Aurélien" last="Dupont">Aurélien Dupont</name>
<name sortKey="Eriksson, Leif A" sort="Eriksson, Leif A" uniqKey="Eriksson L" first="Leif A" last="Eriksson">Leif A. Eriksson</name>
<name sortKey="Fernandez Apico, Martin E" sort="Fernandez Apico, Martin E" uniqKey="Fernandez Apico M" first="Martin E" last="Fernandez-Zapico">Martin E. Fernandez-Zapico</name>
<name sortKey="Fessart, Delphine" sort="Fessart, Delphine" uniqKey="Fessart D" first="Delphine" last="Fessart">Delphine Fessart</name>
<name sortKey="Horberg, Johanna" sort="Horberg, Johanna" uniqKey="Horberg J" first="Johanna" last="Hörberg">Johanna Hörberg</name>
<name sortKey="Hou, Wenyang" sort="Hou, Wenyang" uniqKey="Hou W" first="Wenyang" last="Hou">Wenyang Hou</name>
<name sortKey="Hrstka, Roman" sort="Hrstka, Roman" uniqKey="Hrstka R" first="Roman" last="Hrstka">Roman Hrstka</name>
<name sortKey="Hupp, Ted" sort="Hupp, Ted" uniqKey="Hupp T" first="Ted" last="Hupp">Ted Hupp</name>
<name sortKey="Jansen, Gregor" sort="Jansen, Gregor" uniqKey="Jansen G" first="Gregor" last="Jansen">Gregor Jansen</name>
<name sortKey="Jerome Ajewska, Loydie" sort="Jerome Ajewska, Loydie" uniqKey="Jerome Ajewska L" first="Loydie" last="Jerome-Majewska">Loydie Jerome-Majewska</name>
<name sortKey="Maurel, Marion" sort="Maurel, Marion" uniqKey="Maurel M" first="Marion" last="Maurel">Marion Maurel</name>
<name sortKey="Obacz, Joanna" sort="Obacz, Joanna" uniqKey="Obacz J" first="Joanna" last="Obacz">Joanna Obacz</name>
<name sortKey="Ogier Enis, Eric" sort="Ogier Enis, Eric" uniqKey="Ogier Enis E" first="Eric" last="Ogier-Denis">Eric Ogier-Denis</name>
<name sortKey="Papadodima, Olga" sort="Papadodima, Olga" uniqKey="Papadodima O" first="Olga" last="Papadodima">Olga Papadodima</name>
<name sortKey="Pilalis, Eleftherios" sort="Pilalis, Eleftherios" uniqKey="Pilalis E" first="Eleftherios" last="Pilalis">Eleftherios Pilalis</name>
<name sortKey="Samali, Afshin" sort="Samali, Afshin" uniqKey="Samali A" first="Afshin" last="Samali">Afshin Samali</name>
<name sortKey="Sommerova, Lucia" sort="Sommerova, Lucia" uniqKey="Sommerova L" first="Lucia" last="Sommerova">Lucia Sommerova</name>
<name sortKey="Tavernier, Jan" sort="Tavernier, Jan" uniqKey="Tavernier J" first="Jan" last="Tavernier">Jan Tavernier</name>
<name sortKey="Thomas, David Y" sort="Thomas, David Y" uniqKey="Thomas D" first="David Y" last="Thomas">David Y. Thomas</name>
<name sortKey="Tourneur Arsille, Julien" sort="Tourneur Arsille, Julien" uniqKey="Tourneur Arsille J" first="Julien" last="Tourneur-Marsille">Julien Tourneur-Marsille</name>
<name sortKey="Treton, Xavier" sort="Treton, Xavier" uniqKey="Treton X" first="Xavier" last="Treton">Xavier Treton</name>
</noCountry>
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</affiliations>
</record>
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