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TGF- β /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence
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SYSNO ASEP 0442568 Druh ASEP J - Článek v odborném periodiku Zařazení RIV Záznam nebyl označen do RIV Poddruh J Ostatní články Název TGF- β /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence Tvůrce(i) Kretová, M. (SK)
Sabová, L. (SK)
Hodný, Zdeněk (UMG-J) RID
Bártek, Jiří (UMG-J) RID
Kollárovič, G. (SK)
Nelson, B. D. (SE)
Hubáčková, Soňa (UMG-J) RID
Luciaková, K. (SK)Zdroj.dok. Cellular Signalling. - : Elsevier - ISSN 0898-6568
Roč. 26, č. 12 (2014), s. 2903-2911Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Smad ; Nuclear factor 1 ; Senescence ; Adenine nucleotide translocase-2 ; Transforming growth factor- β ; Oxidative stress Vědní obor RIV EB - Genetika a molekulární biologie CEP GA13-17658S GA ČR - Grantová agentura ČR GA13-17555S GA ČR - Grantová agentura ČR Institucionální podpora UMG-J - RVO:68378050 DOI 10.1016/j.cellsig.2014.08.029 Anotace Oxidative stress and persistent activation of DNA damage response (DDR) are causally involved in the development of cellular senescence, a phenomenon implicated in fundamental (patho)physiological processes such as aging, fetal development and tumorigenesis. Here, we report that adenine nucleotide translocase-2 (ANT2) is consistently down-regulated in all three major forms of cellular senescence: replicative, oncogene-induced and drug-induced, in both normal and cancerous human cells. We previously reported formation of novel NF1/Smad transcription repressor complexes in growth-arrested fibroblasts. Here we show that such complexes form in senescent cells. Mechanistically, binding of the NF1/Smad complexes to the NF1-dependent repressor elements in the ANT2 gene promoter repressed ANT2 expression. Etoposide-induced formation of these complexes and repression of ANT2 were relatively late events co-incident with production and secretion of, and dependent on, TGF-β. siRNA-mediated knock-down of ANT2 in proliferating cells resulted in increased levels of reactive oxygen species (ROS) and activation of the DDR. Knock-down of ANT2, together with etoposide treatment, further intensified ROS production and DNA damage signaling, leading to enhanced apoptosis. Together, our data show that TGF-β-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2015
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