| Attributes | Values |
|---|
| rdf:type
| |
| Description
| - 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.
- 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. (en)
|
| Title
| - TGF- β /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence
- TGF- β /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence (en)
|
| skos:prefLabel
| - TGF- β /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence
- TGF- β /NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence (en)
|
| skos:notation
| - RIV/68378050:_____/14:00442568!RIV15-GA0-68378050
|
| http://linked.open...avai/riv/aktivita
| |
| http://linked.open...avai/riv/aktivity
| - I, P(GA13-17555S), P(GA13-17658S)
|
| http://linked.open...iv/cisloPeriodika
| |
| http://linked.open...vai/riv/dodaniDat
| |
| http://linked.open...aciTvurceVysledku
| |
| http://linked.open.../riv/druhVysledku
| |
| http://linked.open...iv/duvernostUdaju
| |
| http://linked.open...titaPredkladatele
| |
| http://linked.open...dnocenehoVysledku
| |
| http://linked.open...ai/riv/idVysledku
| - RIV/68378050:_____/14:00442568
|
| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - Smad; Nuclear factor 1; Senescence; Adenine nucleotide translocase-2; Transforming growth factor- β; Oxidative stress (en)
|
| http://linked.open.../riv/klicoveSlovo
| |
| http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
|
| http://linked.open...ontrolniKodProRIV
| |
| http://linked.open...i/riv/nazevZdroje
| |
| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
| |
| http://linked.open...iv/tvurceVysledku
| - Hodný, Zdeněk
- Bartek, Jiří
- Hubáčková, Soňa
- Kollárovič, G.
- Kretová, M.
- Luciaková, K.
- Nelson, B. D.
- Sabová, L.
|
| issn
| |
| number of pages
| |
| http://bibframe.org/vocab/doi
| - 10.1016/j.cellsig.2014.08.029
|
![[RDF Data]](/fct/images/sw-rdf-blue.png)
![[cxml]](/fct/images/cxml_doc.png)
![[csv]](/fct/images/csv_doc.png)
![[text]](/fct/images/ntriples_doc.png)
![[turtle]](/fct/images/n3turtle_doc.png)
![[ld+json]](/fct/images/jsonld_doc.png)
![[rdf+json]](/fct/images/json_doc.png)
![[rdf+xml]](/fct/images/xml_doc.png)
![[atom+xml]](/fct/images/atom_doc.png)
![[html]](/fct/images/html_doc.png)