Title :

Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells

Author(s) :

Lopez-Royuela, Nuria [Auteur]
Cellules souches normales et cancéreuses
Rathore, Moeez [Auteur]
Cellules souches normales et cancéreuses
Allende-Vega, Nerea [Auteur]
Cellules souches normales et cancéreuses
Annicotte, Jean-Sébastien [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Fajas, Lluis [Auteur]
Ramachandran, Bindu [Auteur]
Gulick, Tod [Auteur]
Villalba, Martin [Auteur correspondant]
Cellules souches normales et cancéreuses
Institut de recherche en biothérapie [IRB]

Journal title :

International Journal of Biochemistry and Cell Biology

Pages :

253 - 261

Publisher :

Elsevier

Publication date :

2014-08

ISSN :

1357-2725

English keyword(s) :

Oxidative phosphorylation
Mitochondria
ERK5
Sirt1
Anti-oxidant response elements (ARE)

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

Cancer cell metabolism differs from that of non-transformed cells in the same tissue. This specific metabolism gives tumor cells growing advantages besides the effect in increasing anabolism. One of these advantages is ...
Show more >Cancer cell metabolism differs from that of non-transformed cells in the same tissue. This specific metabolism gives tumor cells growing advantages besides the effect in increasing anabolism. One of these advantages is immune evasion mediated by a lower expression of the mayor histocompatibility complex class I molecules. The extracellular-signal-regulated kinase-5 regulates both mayor histocom-patibility complex class I expression and metabolic activity. However, the mechanisms underlying are largely unknown. We show here that extracellular-signal-regulated kinase-5 regulates the transcription of the NADH +-dependent histone deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin 1) in leukemic Jurkat T cells. This involves the activation of the transcription factor myocyte enhancer factor-2 and its binding to the sirt1 promoter. In addition, extracellular-signal-regulated kinase-5 is required for T cell receptor-induced and oxidative stress-induced full Sirtuin 1 expression. Extracellular-signal-regulated kinase-5 induces the expression of promoters containing the antioxi-dant response elements through a Sirtuin 1-dependent pathway. On the other hand, down modulation of extracellular-signal-regulated kinase-5 expression impairs the anti-oxidant response. Notably, the extracellular-signal-regulated kinase-5 inhibitor BIX02189 induces apoptosis in acute myeloid leukemia tumor cells without affecting T cells from healthy donors. Our results unveil a new pathway that modulates metabolism in tumor cells. This pathway represents a promising therapeutic target in cancers with deep metabolic layouts such as acute myeloid leukemia.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL