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DNA-Damage-Induced Type I Interferon Promotes Senescence and Inhibits Stem Cell Function
- Source :
- Cell Reports, Vol 11, Iss 5, Pp 785-797 (2015)
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Summary Expression of type I interferons (IFNs) can be induced by DNA-damaging agents, but the mechanisms and significance of this regulation are not completely understood. We found that the transcription factor IRF3, activated in an ATM-IKKα/β-dependent manner, stimulates cell-autonomous IFN-β expression in response to double-stranded DNA breaks. Cells and tissues with accumulating DNA damage produce endogenous IFN-β and stimulate IFN signaling in vitro and in vivo. In turn, IFN acts to amplify DNA-damage responses, activate the p53 pathway, promote senescence, and inhibit stem cell function in response to telomere shortening. Inactivation of the IFN pathway abrogates the development of diverse progeric phenotypes and extends the lifespan of Terc knockout mice. These data identify DNA-damage-response-induced IFN signaling as a critical mechanism that links accumulating DNA damage with senescence and premature aging.
- Subjects :
- Male
Senescence
Premature aging
DNA damage
Antineoplastic Agents
Apoptosis
Endogeny
Receptor, Interferon alpha-beta
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Cell Line
Mice
Animals
Humans
RNA, Messenger
Intestinal Mucosa
lcsh:QH301-705.5
Telomerase
Transcription factor
Cellular Senescence
Mice, Knockout
Stem Cells
Interferon-beta
Telomere
Antibodies, Neutralizing
Molecular biology
Cell biology
Intestines
Mice, Inbred C57BL
Tamoxifen
lcsh:Biology (General)
NIH 3T3 Cells
Interferon Regulatory Factor-3
RNA Interference
Tumor Suppressor Protein p53
Stem cell
Cell aging
DNA Damage
Signal Transduction
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 11
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....d27ec2ddec1c388b7f4cbaf7280e0182
- Full Text :
- https://doi.org/10.1016/j.celrep.2015.03.069