p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts

Hyun Seok Kim, Eui Ju Yeo, Seong Hoon Park, Joo In Park, Sang Chul Park, Jong Yeon Shin, Min Ju Kim, Soo Jin Oh, Moo Ho Won, Tae Chun Kang, Jae Bong Park, Jaebong Kim, Jong Il Kim, Hyun Yong Lee, Jae Yong Lee

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Hydoxyurea induces senescence-like growth arrest in normal human fibroblasts. p21WAF/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 p21WAF/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 p21WAF/CIP1/SDI1 mRNA was increased by 2.5-fold but that of p21WAF/CIP1/SDI1 protein was not. Our results suggest that increased mRNA stability is the major mechanism of p21WAF/CIP1/SDI1 elevation in the hydroxyurea-induced growth arrest of human fibroblasts.

Original languageEnglish
Pages (from-to)1255-1261
Number of pages7
JournalMechanisms of Ageing and Development
Volume126
Issue number12
DOIs
StatePublished - Dec 2005

Bibliographical note

Funding Information:
This study was supported by a Research Grant from Department of Welfare and Health of Korean Government (Molecular Ageing Research Center) and a grant from Korea Ministry of Science and Technology (Contract #0101029-1-2(2002325)) and Gangwon Province.

Keywords

  • Human fibroblasts
  • Hydroxyurea
  • mRNA stability
  • p21
  • p53
  • Senescence

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