P21<SUP>WAF/CIP1/SDI1</SUP> is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts

  • Kim, HS
  • Yeo, EJ
  • Park, SH
  • Park, JI
  • Park, SC
  • 외 10명
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초록

Hydoxyurea induces senescence-like growth arrest in normal human fibroblasts. p21(WAF/CIP1/SDI1), a cyclin dependent kinase inhibitor, was found to be upregulated during this growth arrest. Levels of p21(WAF/CIP1/SDI1) protein and mRNA were increased nine-fold by hydroxyurea in these cells. In order to determine whether p21(WAF/CIP1/SDI1) mRNA is increased by hydroxyurea at the transcriptional level, human fibroblast cells were transfected with reporter constructs containing a p21(WAF/CIP1/SDI1) promoter fragment and then treated with hydroxyurea. The luciferase activities in the reporter-transfected fibroblast cells were not increased by hydroxyurea, indicating that p21(WAF/CIP1/SDI1) transcription was not elevated by hydroxyurea. The half-life of the p21(WAF/CIP1/SDI1) mRNA was increased by 2.5-fold but that of p21(WAF/CIP1/SDI1) protein was not. Our results suggest that increased mRNA stability is the major mechanism of p21(WAF/CIP1/SDI1) elevation in the hydroxyurea-induced growth arrest of human fibroblasts. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

키워드

hydroxyureap53p21(WAF/CIP1/SDI1)mRNA stabilityhuman fibroblastssenescenceP21(WAF1/CIP1) EXPRESSIONCARCINOMA CELLSUV-LIGHTSTABILIZATIONINDUCTIONARRESTGROWTHACTIVATIONINHIBITORPROMOTER
제목
P21<SUP>WAF/CIP1/SDI1</SUP> is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts
저자
Kim, HSYeo, EJPark, SHPark, JIPark, SCShin, JYKim, MJOh, SJWon, MHKang, TCPark, JBKim, JKim, JILee, HYLee, JY
DOI
10.1016/j.mad.2005.07.002
발행일
2005-12
유형
Article
저널명
Mechanisms of Ageing and Development
126
12
페이지
1255 ~ 1261