Estrogen prevents senescence through induction of WRN, Werner syndrome protein.
Werner syndrome is a well-known human progeria. It has been revealed that loss of human WRN is a causal factor of this disease. Since pathological features of Werner syndrome resemble those of menopausal women and become apparent during puberty, we examined the effect of estrogen on WRN gene expression. Here, we reveal that WRN is induced by estrogen but not testosterone. Treatment with estrogen can induce WRN expression at the transcription and translation level in a human breast cell line. Forced expression of the estrogen receptor can restore the responsiveness of WRN to estrogen in a non-responsive cell line. Treatment with estrogen can block DNA damage-induced senescence. Moreover, WRN is suppressed by ATR that is activated by DNA damage, whereas WRN can be induced by ATR elimination. Our results suggest that WRN is essential for prevention of senescence. In addition, our results imply that the reduction of WRN in menopause could be an important factor for menopausal syndrome.
Lee
Su-Jin
SJ
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Republic of Korea.
Lee
Sun-Hye
SH
Ha
Nam-Chul
NC
Park
Bum-Joon
BJ
D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002648:Child; D004249:DNA Damage; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005090:Exodeoxyribonucleases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053484:RecQ Helicases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014898:Werner Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071657:Werner Syndrome Helicase
D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D012333:RNA, Messenger; D013739:Testosterone; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase