Chronic NF-kappaB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response
| dc.contributor.author | Batsi, C. | en |
| dc.contributor.author | Markopoulou, S. | en |
| dc.contributor.author | Vartholomatos, G. | en |
| dc.contributor.author | Georgiou, I. | en |
| dc.contributor.author | Kanavaros, P. | en |
| dc.contributor.author | Gorgoulis, V. G. | en |
| dc.contributor.author | Marcu, K. B. | en |
| dc.contributor.author | Kolettas, E. | en |
| dc.date.accessioned | 2015-11-24T19:30:34Z | |
| dc.date.available | 2015-11-24T19:30:34Z | |
| dc.identifier.issn | 1872-6216 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/23125 | |
| dc.rights | Default Licence | - |
| dc.subject | *Cell Aging | en |
| dc.subject | Cell Proliferation | en |
| dc.subject | Cells, Cultured | en |
| dc.subject | Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism | en |
| dc.subject | *DNA Damage | en |
| dc.subject | Fibroblasts/cytology/*metabolism | en |
| dc.subject | Humans | en |
| dc.subject | NF-kappa B/genetics/*metabolism | en |
| dc.subject | Oncogene Protein p21(ras)/genetics/*metabolism | en |
| dc.subject | *Signal Transduction | en |
| dc.subject | Tumor Suppressor Protein p53/genetics/metabolism | en |
| dc.title | Chronic NF-kappaB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response | en |
| heal.abstract | Normal cells divide for a limited number of generations, after which they enter a state of irreversible growth arrest termed replicative senescence. While replicative senescence is due to telomere erosion, normal human fibroblasts can undergo stress-induced senescence in response to oncogene activation, termed oncogene-induced senescence (OIS). Both, replicative and OIS, initiate a DNA damage checkpoint response (DDR) resulting in the activation of the p53-p21(Cip1/Waf1) pathway. However, while the nuclear factor-kappaB (NF-kappaB) signaling pathway has been implicated in DDR, its role in OIS has not been investigated. Here, we show that oncogenic Ha-RasV12 promoted premature senescence of IMR-90 normal human diploid fibroblasts by activating DDR, hence verifying the classical model of OIS. However, enforced expression of a constitutively active IKKbeta T-loop mutant protein (IKKbetaca), significantly delayed OIS of IMR-90 cells by suppressing Ha-RasV12 instigated DDR. Thus, our experiments have uncovered an important selective advantage in chronically activating canonical NF-kappaB signaling to overcome the anti-proliferative OIS response of normal primary human fibroblasts. | en |
| heal.access | campus | - |
| heal.fullTextAvailability | TRUE | - |
| heal.identifier.primary | 10.1016/j.mad.2009.04.002 | - |
| heal.identifier.secondary | http://www.ncbi.nlm.nih.gov/pubmed/19406145 | - |
| heal.identifier.secondary | http://ac.els-cdn.com/S0047637409000530/1-s2.0-S0047637409000530-main.pdf?_tid=045acd5d0694861db1d623c4b3461a6e&acdnat=1333090268_deafaca60287666091d66bda238881d8 | - |
| heal.journalName | Mech Ageing Dev | en |
| heal.journalType | peer-reviewed | - |
| heal.language | en | - |
| heal.publicationDate | 2009 | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής | el |
| heal.type | journalArticle | - |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.type.en | Journal article | en |
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