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Title

The thyroid hormone receptor β induces DNA damage and premature senescence

AuthorsZambrano, Alberto ; García-Carpizo, Verónica ; Gallardo, M. Esther ; Villamuera, Raquel; Gómez-Ferrería, María Ana ; Pascual, Ángel ; Buisine, Nicolas; Sachs, Laurent M.; Garesse, Rafael ; Aranda, Ana
Issue Date2014
PublisherRockefeller University Press
CitationJournal of Cell Biology 204(1): 129-146 (2014)
AbstractThere is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate- activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double- strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism. © 2014 Zambrano et al.
DescriptionThis article is distributed under the terms of a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license).
Publisher version (URL)http://dx.doi.org/10.1083/jcb.201305084
URIhttp://hdl.handle.net/10261/103757
DOI10.1083/jcb.201305084
Identifiersdoi: 10.1083/jcb.201305084
issn: 0021-9525
e-issn: 1540-8140
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