Title :

Delta-lactoferrin induces cell death via the mitochondrial death signaling pathway by upregulating bax expression

Author(s) :

Hardivillé, Stéphan [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Escobar-Ramirez, Adelma [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Pina-Canceco, Soccoro [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Elass, Elisabeth [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Pierce, Annick [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]

Journal title :

Biometals. An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine

Abbreviated title :

Biometals

Volume number :

27

Pages :

875-889

Publication date :

2014-10

ISSN :

1572-8773

English keyword(s) :

fas Receptor
Promoter Regions, Genetic
Up-Regulation
Humans
Transcriptional Activation
bcl-2-Associated X Protein
Lactoferrin
Mitochondria
MCF-7 Cells
Site-directed mutagenesis
Protein Isoforms
HEK293 Cells
HeLa Cells
Acylation
Apoptosis

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Delta-lactoferrin (∆Lf) is a transcription factor belonging to the lactoferrin family, the expression of which inhibits cell proliferation and leads to Skp1 and DcpS gene transactivation. In this study, we showed that ∆Lf ...
Show more >Delta-lactoferrin (∆Lf) is a transcription factor belonging to the lactoferrin family, the expression of which inhibits cell proliferation and leads to Skp1 and DcpS gene transactivation. In this study, we showed that ∆Lf expression also induces cell death via apoptosis in HEK 293 and MCF7 cells using a cell viability assay and DNA fragmentation. Western blot analyses showed that apoptosis was caspase-9, 7 and 8 dependent. Proteolytic cleavage of the endonuclease PARP was significantly increased. The levels of expression of Bcl family members were detected by immunochemistry and showed that the Bcl-xl/Bax and Bcl-2/Bax protein ratios were decreased. We determined that the pro-apoptotic effects of ∆Lf are mainly mediated by the activation of the mitochondria-dependent death-signaling pathway. Apoptosis induction by ∆Lf is concomitant with increased cellular levels of Bax protein. Analysis of the Bax promoter region detected a ∆Lf response element located at -155 bp from the transcription start site. Both luciferase reporter gene and chromatin immunoprecipitation assays confirmed that ∆Lf interacts in vitro and in vivo specifically with this sequence. Its deletion, realized using directed mutagenesis, totally abolished ∆Lf transcriptional activity, identifying it as a ∆Lf-responsive element. These results indicate that the Bax gene is a novel ∆Lf target. Moreover we also showed that the O-GlcNAc/P interplay, which controls ∆Lf transcriptional activity, modulates Bax transactivation.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Chemical Glycobiology

Submission date :

2020-02-12T15:11:06Z
2021-05-07T10:24:30Z