Clic4, a novel protein that sensitizes β-cells to apoptosis.

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_F1F8D030E49F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Clic4, a novel protein that sensitizes β-cells to apoptosis.
Périodique
Molecular Metabolism
Auteur(s)
Patel D., Ythier D., Brozzi F., Eizirik D.L., Thorens B.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Statut éditorial
Publié
Date de publication
2015
Volume
4
Numéro
4
Pages
253-264
Langue
anglais
Résumé
OBJECTIVES: Chloride intracellular channel protein 4 (Clic4) is a ubiquitously expressed protein involved in multiple cellular processes including cell-cycle control, cell differentiation, and apoptosis. Here, we investigated the role of Clic4 in pancreatic β-cell apoptosis.
METHODS: We used βTC-tet cells and islets from β-cell specific Clic4 knockout mice (βClic4KO) and assessed cytokine-induced apoptosis, Bcl2 family protein expression and stability, and identified Clic4-interacting proteins by co-immunoprecipitation and mass spectrometry analysis.
RESULTS: We show that cytokines increased Clic4 expression in βTC-tet cells and in mouse islets and siRNA-mediated silencing of Clic4 expression in βTC-tet cells or its genetic inactivation in islets β-cells, reduced cytokine-induced apoptosis. This was associated with increased expression of Bcl-2 and increased expression and phosphorylation of Bad. Measurement of Bcl-2 and Bad half-lives in βTC-tet cells showed that Clic4 silencing increased the stability of these proteins. In primary islets β-cells, absence of Clic4 expression increased Bcl-2 and Bcl-xL expression as well as expression and phosphorylation of Bad. Mass-spectrometry analysis of proteins co-immunoprecipitated with Clic4 from βTC-tet cells showed no association of Clic4 with Bcl-2 family proteins. However, Clic4 co-purified with proteins from the proteasome suggesting a possible role for Clic4 in regulating protein degradation.
CONCLUSIONS: Collectively, our data show that Clic4 is a cytokine-induced gene that sensitizes β-cells to apoptosis by reducing the steady state levels of Bcl-2, Bad and phosphorylated Bad.
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/06/2015 11:18
Dernière modification de la notice
09/05/2019 3:20
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