Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors
العنوان: | Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors |
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المؤلفون: | M. Aiman Mohtar, Reynald Gillet, Daniel Thomas, Pierre-Jean Le Reste, Federica G. Centonze, Sophie Chat, Ted R. Hupp, Luc Negroni, Aeid Igbaria, Raphael Pineau, Daria Sicari, Eric Chevet |
المساهمون: | Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Edinburgh, Ben-Gurion University of the Negev (BGU), This work was funded by grants from Institut National de la Santé et de la Recherche Médicale (INSERM‐U1242), Institut National du Cancer (INCa, PLBIO18, PLBIO19, PLBIO20), Fondation pour la Recherche Médicale (FRM, équipe labellisée 2018, DEQ20180339169), Agence National de la Recherche (ANR, ERANET ERAAT), MSCA RISE‐734749 (INSPIRED), Cancéropôle Grand Ouest (Gliotreat) grants to EC, the BBSRC UK (EM, BB/C511599/1, and BB/J00751X/1) and UKM Fellowship and Ministry of Higher Education (MOHE) of Malaysia KPT(BS)870809015063 (MAM). DS was supported by an AIRC #22319 fellowship for abroad., ANR-17-RAR3-0003,ERAAT,Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency(2017), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), HAL UR1, Admin, Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency - - ERAAT2017 - ANR-17-RAR3-0003 - E-RARE - VALID |
المصدر: | EMBO Reports EMBO Reports, 2021, 22 (5), pp.e51412. ⟨10.15252/embr.202051412⟩ EMBO Reports, EMBO Press, 2021, 22 (5), pp.e51412. ⟨10.15252/embr.202051412⟩ Sicari, D, Centronze, F G, Pineau, R, Le Reste, P-J, Negroni, L, Chat, S, Mohtar, M A, Thomas, D, Gillet, R, Hupp, T R, Chevet, E & Igbaria, A 2021, ' Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors ', EMBO Reports . https://doi.org/10.15252/embr.202051412Test |
بيانات النشر: | HAL CCSD, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | AGR2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endoplasmic-reticulum-associated protein degradation, Biochemistry, Article, law.invention, 03 medical and health sciences, Mice, 0302 clinical medicine, Cytosol, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Genetics, Selective advantage, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, cancer, Translation & Protein Quality, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Organelles, 0303 health sciences, Chemistry, Endoplasmic reticulum, Proteins, Endoplasmic Reticulum-Associated Degradation, Articles, ERAD, Endoplasmic Reticulum Stress, 3. Good health, Cell biology, endoplasmic reticulum, Proteostasis, Unfolded protein response, Suppressor, reflux, ER stress, 030217 neurology & neurosurgery |
الوصف: | In the past decades, many studies reported the presence of endoplasmic reticulum (ER)‐resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain‐of‐cytosolic functions—a phenomenon we name ER to Cytosol Signaling (ERCYS). Endoplasmic Reticulum (ER) stress in cancer cells causes a subset of ER proteins to escape to the cytosol where they bind and inhibit key signaling pathways to increase cancer cell fitness. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1469-221X 1469-3178 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c16e1dca854f240c2c0540dbaec04d47Test https://hal.science/hal-03194503Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....c16e1dca854f240c2c0540dbaec04d47 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 1469221X 14693178 |
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