P21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts

被引：14
作者：
Kim, HS
Yeo, EJ
Park, SH
Park, JI
Park, SC
Shin, JY
Kim, MJ
Oh, SJ
Won, MH
Kang, TC
Park, JB
Kim, J
Kim, JI
Lee, HY
Lee, JY
机构：
[1] Hallym Univ, Coll Med, Dept Biochem, Chunchon 200702, Gangwon, South Korea
[2] Gachun Univ, Coll Med, Dept Biochem, Ganghwa, South Korea
[3] Dong A Univ, Coll Med, Dept Biochem, Pusan, South Korea
[4] Seoul Natl Univ, Sch Med, Dept Biochem & Mol Biol, Seoul, South Korea
[5] Gangwon Univ, Sch Biotechnol & Bioengn, Chunchon, South Korea
[6] Hallym Univ, Coll Med, Dept Anat, Chunchon 200702, Gangwon, South Korea
来源：
MECHANISMS OF AGEING AND DEVELOPMENT | 2005年 / 126卷 / 12期
关键词：
hydroxyurea; p53; p21(WAF/CIP1/SDI1); mRNA stability; human fibroblasts; senescence;
D O I：
10.1016/j.mad.2005.07.002
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
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收藏
页码：1255 / 1261
页数：7
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