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

doi:10.1016/j.mad.2005.07.002

p21^{WAF/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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	1255-1261
Number of pages	7
Journal	Mechanisms of Ageing and Development
Volume	126
Issue number	12
DOIs	https://doi.org/10.1016/j.mad.2005.07.002
State	Published - 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
Senescence
mRNA stability
p21
p53

Access to Document

10.1016/j.mad.2005.07.002

Cite this

Kim, H. S., Yeo, E. J., Park, S. H., Park, J. I., Park, S. C., Shin, J. Y., Kim, M. J., Oh, S. J., Won, M. H., Kang, T. C., Park, J. B., Kim, J., Kim, J. I., Lee, H. Y., & Lee, J. Y. (2005). p21^{WAF/CIP1/SDI1} is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts. Mechanisms of Ageing and Development, 126(12), 1255-1261. https://doi.org/10.1016/j.mad.2005.07.002

@article{4857e75ea447434ea968e39ae6195627,

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

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.",

keywords = "Human fibroblasts, Hydroxyurea, Senescence, mRNA stability, p21, p53",

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

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.",

year = "2005",

month = dec,

doi = "10.1016/j.mad.2005.07.002",

language = "English",

volume = "126",

pages = "1255--1261",

journal = "Mechanisms of Ageing and Development",

issn = "0047-6374",

publisher = "Elsevier Ireland Ltd",

number = "12",

}

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 2005, 'p21^{WAF/CIP1/SDI1} is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts', Mechanisms of Ageing and Development, vol. 126, no. 12, pp. 1255-1261. https://doi.org/10.1016/j.mad.2005.07.002

TY - JOUR

T1 - p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts

AU - Kim, Hyun Seok

AU - Yeo, Eui Ju

AU - Park, Seong Hoon

AU - Park, Joo In

AU - Park, Sang Chul

AU - Shin, Jong Yeon

AU - Kim, Min Ju

AU - Oh, Soo Jin

AU - Won, Moo Ho

AU - Kang, Tae Chun

AU - Park, Jae Bong

AU - Kim, Jaebong

AU - Kim, Jong Il

AU - Lee, Hyun Yong

AU - Lee, Jae Yong

N1 - 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.

PY - 2005/12

Y1 - 2005/12

N2 - 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.

AB - 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.

KW - Human fibroblasts

KW - Hydroxyurea

KW - Senescence

KW - mRNA stability

KW - p21

KW - p53

UR - https://www.scopus.com/pages/publications/27644453248

U2 - 10.1016/j.mad.2005.07.002

DO - 10.1016/j.mad.2005.07.002

M3 - Article

C2 - 16111738

AN - SCOPUS:27644453248

SN - 0047-6374

VL - 126

SP - 1255

EP - 1261

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

IS - 12

ER -