S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biochemistry & Molecular Biology (생화학교실) Journal Papers (저널논문_생화학교실)
p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts
- Kim, Hyun-Seok; Yeo, Eui-ju; Park, Seong-Hoon; Park, Joo-In; Park, Sang-Chul; Shin, Jong-Yeon; Kim, Min-Ju; Oh, Soo-Jin; Won, Moo-Ho; Kang, Tae-Chun; Park, Jae-Bong; Kim, Jaebong; Kim, Jong-Il; Lee, Hyun-Yong; Lee, Jae-Yong
- Issue Date
- Mech Ageing Dev. 2005 Dec;126(12):1255-61. Epub 2005 Aug 18.
- Blotting, Northern; Blotting, Western; Cell Aging; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p21/*biosynthesis; Dose-Response Relationship, Drug; Fibroblasts/*cytology/metabolism; *Gene Expression Regulation; Genes, Reporter; Humans; Hydroxyurea/metabolism/*pharmacology; Luciferases/metabolism; Nucleic Acid Conformation; Plasmids/metabolism; Promoter Regions, Genetic; RNA, Messenger/*metabolism; Time Factors; Transcription, Genetic; Transfection; *Up-Regulation
- 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.
- 0047-6374 (Print)
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