RRM2B suppresses activation of the oxidative stress pathway and is Up-regulated by P53 during senescence

Mei Ling Kuo, Alexander J. Sy, Lijun Xue, Martin Chi, Michelle T. Michelle, Terence Yen, Mei Iok Chiang, Lufen Chang, Peiguo Chu, Yun Yen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

RRM2B is the DNA damage-inducible small subunit of ribonucleotide reductase, the rate-limiting enzyme in de novo deoxyribonucleoside triphosphate synthesis. Although RRM2B is implicated in DNA repair and the maintenance of mitochondrial DNA content, the regulation and function of RRM2B in senescence have not been previously established. Here, we show that RRM2B is highly induced in a p53-dependent manner during senescence in primary human fibroblast IMR90 cells and is expressed at higher levels in senescent precancerous human prostatic intraepithelial neoplasm lesions compared to adjacent normal prostate glands. Paradoxically, silencing RRM2B expression leads to an increase in the level of reactive oxygen species, mitochondrial membrane depolarization, and premature senescence in a p38MAPK-and p53-dependent manner in young fibroblasts. Consistently, induction of senescence is accelerated in Rrm2b deficient mouse embryo fibroblasts. Our data demonstrate that RRM2B is induced by stress signals prior to the onset of senescence and prevents premature oxidative stress-induced senescence.

Original languageEnglish
Article number822
JournalScientific Reports
Volume2
DOIs
Publication statusPublished - Nov 22 2012

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Oxidative Stress
Fibroblasts
Prostatic Intraepithelial Neoplasia
Deoxyribonucleosides
Ribonucleotide Reductases
Mitochondrial Membranes
Mitochondrial DNA
DNA Repair
DNA Damage
Prostate
Reactive Oxygen Species
Embryonic Structures
Maintenance
Enzymes

ASJC Scopus subject areas

  • General

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RRM2B suppresses activation of the oxidative stress pathway and is Up-regulated by P53 during senescence. / Kuo, Mei Ling; Sy, Alexander J.; Xue, Lijun; Chi, Martin; Michelle, Michelle T.; Yen, Terence; Chiang, Mei Iok; Chang, Lufen; Chu, Peiguo; Yen, Yun.

In: Scientific Reports, Vol. 2, 822, 22.11.2012.

Research output: Contribution to journalArticle

Kuo, Mei Ling ; Sy, Alexander J. ; Xue, Lijun ; Chi, Martin ; Michelle, Michelle T. ; Yen, Terence ; Chiang, Mei Iok ; Chang, Lufen ; Chu, Peiguo ; Yen, Yun. / RRM2B suppresses activation of the oxidative stress pathway and is Up-regulated by P53 during senescence. In: Scientific Reports. 2012 ; Vol. 2.
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