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The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorMANSIER, Olivier
dc.contributor.authorPROUZET-MAULÉON, Valérie
dc.contributor.authorJÉGOU, Gwénaële
dc.contributor.authorBARROSO, Kim
dc.contributor.authorRAYMUNDO, Diana Pelizzari
dc.contributor.authorCHAUVEAU, Aurélie
hal.structure.identifierBiothérapies des maladies génétiques et cancers
dc.contributor.authorDUMAS, Pierre-Yves
dc.contributor.authorLAGARDE, Valérie
dc.contributor.authorTURCQ, Béatrice
dc.contributor.authorPASQUET, Jean-Max
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorVIALLARD, Jean-François
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJAMES, Chloé
dc.contributor.authorPRALORAN, Vincent
dc.contributor.authorVOUTETAKIS, Konstantinos
dc.contributor.authorCHATZIIOANNOU, Aristotelis
dc.contributor.authorMAHON, François-Xavier
dc.contributor.authorCHEVET, Eric
dc.contributor.authorLIPPERT, Eric
dc.date.accessioned2020-11-10T10:51:21Z
dc.date.available2020-11-10T10:51:21Z
dc.date.issued2019-12
dc.identifier.issn2072-6694en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/12191
dc.description.abstractEnBACKGROUND: Mutations in CALR observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) pathway. However, little is known on the impact of those variant CALR proteins on endoplasmic reticulum (ER) homeostasis. METHODS: The impact of the expression of Wild Type (WT) or mutant CALR on ER homeostasis was assessed by quantifying the expression level of Unfolded Protein Response (UPR) target genes, splicing of X-box Binding Protein 1 (XBP1), and the expression level of endogenous lectins. Pharmacological and molecular (siRNA) screens were used to identify mechanisms involved in CALR mutant proteins degradation. Coimmunoprecipitations were performed to define more precisely actors involved in CALR proteins disposal. RESULTS: We showed that the expression of CALR mutants alters neither ER homeostasis nor the sensitivity of hematopoietic cells towards ER stress-induced apoptosis. In contrast, the expression of CALR variants is generally low because of a combination of secretion and protein degradation mechanisms mostly mediated through the ER-Associated Degradation (ERAD)-proteasome pathway. Moreover, we identified a specific ERAD network involved in the degradation of CALR variants. CONCLUSIONS: We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectArticle RECHERCHE
dc.subject.enCalreticulin
dc.subject.enEndoplasmic reticulum
dc.subject.enERAD
dc.subject.enMPN
dc.title.enThe Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation
dc.typeArticle de revueen_US
dc.identifier.doi10.3390/cancers11121921en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed31810292en_US
bordeaux.journalCancersen_US
bordeaux.volume11en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue12en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cancers&rft.date=2019-12&rft.volume=11&rft.issue=12&rft.eissn=2072-6694&rft.issn=2072-6694&rft.au=MANSIER,%20Olivier&PROUZET-MAUL%C3%89ON,%20Val%C3%A9rie&J%C3%89GOU,%20Gw%C3%A9na%C3%ABle&BARROSO,%20Kim&RAYMUNDO,%20Diana%20Pelizzari&rft.genre=article


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