Format

Send to

Choose Destination
Cell Signal. 2012 Mar;24(3):708-17. doi: 10.1016/j.cellsig.2011.11.004. Epub 2011 Nov 13.

Human telomerase represses ROS-dependent cellular responses to Tumor Necrosis Factor-α without affecting NF-κB activation.

Author information

1
de Duve Institute, Faculty of Pharmacy and Biomedical Sciences, Catholic University of Louvain, Brussels, Belgium. marina.mattiussi@uclouvain.be

Abstract

In addition to its well-established role in telomere synthesis, telomerase exerts non-canonical functions that may promote cancer and stem cell survival, notably by lowering reactive oxygen species (ROS) levels and acting as transcriptional cofactor in Wnt-β-catenin signaling pathway. We investigated the impact of telomerase on ROS-dependent and -independent cellular responses to Tumor Necrosis Factor-α (TNF-α), a potent inducer of endogenous ROS production and activator of NF-κB signaling pathway. Strikingly, telomerase overexpression in normal human fibroblasts treated with TNF-α strongly repressed ROS-dependent activation of both ERK1/2 mitogen-activated protein kinases and cell death. Telomerase overexpression also considerably diminished TNF-α-induced transcription of SOD2 Superoxide Dismutase 2 gene by reducing ROS contribution to SOD2 gene induction, both in normal fibroblasts and in cancer cells. Conversely, telomerase did not impair TNF-α-induced transcription of various ROS-insensitive NF-κB target genes. These data were in apparent contrast with the striking observation that telomerase overexpression induced strong constitutive nuclear accumulation of NF-κBp65. Accumulated NF-κBp65, however, lacked Ser-536 activating phosphorylation, was not associated with global constitutive NF-κB activation and did not impair subsequent nuclear translocation of phosphorylated NF-κBp65 in response to TNF-α. Our results demonstrate that human telomerase represses ROS-dependent intracellular signaling and gene induction in response to TNF-α.

PMID:
22108091
DOI:
10.1016/j.cellsig.2011.11.004
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center