DNA-Damage-Induced Type I Interferon Promotes Senescence and Inhibits Stem Cell Function

被引：204

作者：

Yu, Qiujing ^{[1
]}

Katlinskaya, Yuliya V. ^{[1
]}

Carbone, Christopher J. ^{[1
]}

Zhao, Bin ^{[1
]}

Katlinski, Kanstantsin V. ^{[1
]}

Zheng, Hui ^{[1
]}

Guha, Manti ^{[1
]}

Li, Ning ^{[1
]}

Chen, Qijun ^{[2
]}

Yang, Ting ^{[2
]}

Lengner, Christopher J. ^{[1
]}

Greenberg, Roger A. ^{[2
,3
]}

Johnson, F. Brad ^{[2
]}

Fuchs, Serge Y. ^{[1
]}

机构：

[1] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Abramson Family Canc Res Inst,Basser Res Ctr BRCA, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Dept Canc Biol, Abramson Family Canc Res Inst,Basser Res Ctr BRCA, Philadelphia, PA 19104 USA

来源：

CELL REPORTS | 2015年 / 11卷 / 05期

关键词：

TELOMERE DYSFUNCTION; DEPENDENT PHOSPHORYLATION; REGULATORY FACTOR-3; SECRETORY PHENOTYPE; ANTIVIRAL DEFENSE; TUMOR SUPPRESSION; GENE-EXPRESSION; CYTOSOLIC DNA; CANCER; ACTIVATION;

D O I：

10.1016/j.celrep.2015.03.069

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-IKK alpha/beta-dependent manner, stimulates cell-autonomous IFN-beta expression in response to double-stranded DNA breaks. Cells and tissues with accumulating DNA damage produce endogenous IFN-beta 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.

引用

页码：785 / 797

页数：13

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