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p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts
Cited 13 time in
Web of Science
Cited 15 time in Scopus
- Authors
- Issue Date
- 2005-08-23
- Publisher
- Elsevier
- Citation
- Mech Ageing Dev. 2005 Dec;126(12):1255-61. Epub 2005 Aug 18.
- Keywords
- Blotting, Northern ; Blotting, Western ; Cell Aging ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p21/*biosynthesis ; Dose-Response Relationship, Drug ; Fibroblasts/*cytology/metabolism ; Genes, Reporter ; Humans ; Hydroxyurea/metabolism/*pharmacology ; Luciferases/metabolism ; Nucleic Acid Conformation ; Plasmids/metabolism ; Promoter Regions, Genetic ; RNA, Messenger/*metabolism ; Time Factors ; Transcription, Genetic ; Transfection ; Gene Expression Regulation ; Up-Regulation
- Abstract
- 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.
- ISSN
- 0047-6374 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16111738
https://hdl.handle.net/10371/26283
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