Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	The expression of myeloproliferative neoplasm-associated calreticulin variants depends on the functionality of er-associated degradation
Δημιουργός/Συγγραφέας:	Mansier O. Prouzet-Mauléon V. Jégou G. Barroso K. Pelizzari Raymundo D. Chauveau A. Pierre-Yves D. Lagarde V. Turcq B. Jean-Max P. Jean-François V. James C. Praloran V. [EL] Βουτετάκης, Κωνσταντίνος[EN] Voutetakis, Konstantinos [EL] Χατζηιωάννου, Αριστοτέλης[EN] Chatziioannou, Aristotelis François-Xavier M. Chevet E. Lippert E.
Εκδότης:	MDPI AG
Ημερομηνία:	2019
Γλώσσα:	Αγγλικά
ISSN:	2072-6694
DOI:	10.3390/cancers11121921
Περίληψη:	Background: 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.
Τίτλος πηγής δημοσίευσης:	Cancers
Τόμος/Κεφάλαιο:	11
Τεύχος:	12
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens)
Λέξεις-Κλειδιά:	Calreticulin Endoplasmic reticulum ERAD MPN
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2019, MDPI AG. All rights reserved.
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	ITN-675448; 2014-E02; Ligue Contre le Cancer; Institut National Du Cancer, INCa Funding: This work was supported by grants from INCa-Cancéropôle GSO (N°2014-E02) and Ligue Contre le Cancer to EL and Institut National du Cancer (INCa PLBIO), la Ligue Contre le Cancer and EU H2020 MSCA ITN-675448 (TRAINERS) to EC. OM was supported by a PhD fellowship from the French Research and Education ministry.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο