. . . . "I, P(GA13-17555S), P(GA13-17658S)" . . "Luciakov\u00E1, K." . "TGF- \u03B2 /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence"@en . "Bartek, Ji\u0159\u00ED" . "TGF- \u03B2 /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence" . "Koll\u00E1rovi\u010D, G." . "RIV/68378050:_____/14:00442568!RIV15-GA0-68378050" . "Kretov\u00E1, M." . "26" . "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-\u03B2. 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-\u03B2-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence."@en . . "9"^^ . . . "TGF- \u03B2 /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence" . . . "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-\u03B2. 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-\u03B2-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence." . . "Cellular Signalling" . . "Nelson, B. D." . . . "Hodn\u00FD, Zden\u011Bk" . "0898-6568" . "3"^^ . . "50213" . . . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . "Smad; Nuclear factor 1; Senescence; Adenine nucleotide translocase-2; Transforming growth factor- \u03B2; Oxidative stress"@en . "Sabov\u00E1, L." . "RIV/68378050:_____/14:00442568" . . "TGF- \u03B2 /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence"@en . . "8"^^ . "Hub\u00E1\u010Dkov\u00E1, So\u0148a" . . "12" . . "[C2A6DBF081BC]" . "10.1016/j.cellsig.2014.08.029" . .