Regulation of the p21(Sdi1/Cip1/Waf1) DNA synthesis inhibitor in senescent human diploid fibroblasts

Ryan S. Robetorye, James R. Smith

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A large body of evidence has demonstrated that normal human fibroblasts have a limited division potential in culture and underwent senescence, a process whereby cells became arrested in the G 1 phase of the cell cycle and overexpressed a DNA synthesis inhibitor(s). Cyclin-dependent kinase two (Cdk2) is required for the promotion of the G 1-to-S phase transition in human cells. Senescent fibroblasts contain intact cyclin-Cdk2 complexes but cannot induce Cdk2 protein kinase activity in response to mitogen stimulation. Recently, we cloned p21(Sdi1), a potent inhibitor of DNA synthesis and Cdk2 kinase activity, from a senescent cell cDNA library and demonstrated that it was expressed at significantly higher levels in senescent cells than actively proliferating cells. In contrast to actively dividing cells, mitogen-stimulated senescent cells do not down-regulate the expression of p21(Sdi1) and do not express late G 1 phase gene products that are required for entry into S phase. We suggest that the inability of mitogen-stimulated senescent cells to down-regulate p21(Sdi1) levels contributes to the resulting lack of late G 1 gene expression and failure to traverse the G 1/S phase boundary.

Original languageEnglish (US)
Pages (from-to)315-329
Number of pages15
JournalCanadian Journal on Aging
Volume15
Issue number2
StatePublished - Jun 1996
Externally publishedYes

Fingerprint

Nucleic Acid Synthesis Inhibitors
Diploidy
Fibroblasts
regulation
promotion
S Phase
Mitogens
lack
evidence
Down-Regulation
Cyclin-Dependent Kinase 2
Cyclins
Cyclin-Dependent Kinases
Phase Transition
Gene Library
Cell Cycle
Phosphotransferases
Gene Expression

Keywords

  • Cdk inhibitor
  • Cdk2
  • cell cycle
  • DNA synthesis
  • p21(Sdi1)

ASJC Scopus subject areas

  • Aging

Cite this

Regulation of the p21(Sdi1/Cip1/Waf1) DNA synthesis inhibitor in senescent human diploid fibroblasts. / Robetorye, Ryan S.; Smith, James R.

In: Canadian Journal on Aging, Vol. 15, No. 2, 06.1996, p. 315-329.

Research output: Contribution to journalArticle

@article{bbf6181f2fff465b9aabd0f300361b9a,
title = "Regulation of the p21(Sdi1/Cip1/Waf1) DNA synthesis inhibitor in senescent human diploid fibroblasts",
abstract = "A large body of evidence has demonstrated that normal human fibroblasts have a limited division potential in culture and underwent senescence, a process whereby cells became arrested in the G 1 phase of the cell cycle and overexpressed a DNA synthesis inhibitor(s). Cyclin-dependent kinase two (Cdk2) is required for the promotion of the G 1-to-S phase transition in human cells. Senescent fibroblasts contain intact cyclin-Cdk2 complexes but cannot induce Cdk2 protein kinase activity in response to mitogen stimulation. Recently, we cloned p21(Sdi1), a potent inhibitor of DNA synthesis and Cdk2 kinase activity, from a senescent cell cDNA library and demonstrated that it was expressed at significantly higher levels in senescent cells than actively proliferating cells. In contrast to actively dividing cells, mitogen-stimulated senescent cells do not down-regulate the expression of p21(Sdi1) and do not express late G 1 phase gene products that are required for entry into S phase. We suggest that the inability of mitogen-stimulated senescent cells to down-regulate p21(Sdi1) levels contributes to the resulting lack of late G 1 gene expression and failure to traverse the G 1/S phase boundary.",
keywords = "Cdk inhibitor, Cdk2, cell cycle, DNA synthesis, p21(Sdi1)",
author = "Robetorye, {Ryan S.} and Smith, {James R.}",
year = "1996",
month = "6",
language = "English (US)",
volume = "15",
pages = "315--329",
journal = "Canadian Journal on Aging/La Revue canadienne du vieillissment/Canadian Public Policy/Analyse de Politiques",
issn = "0714-9808",
publisher = "Cambridge University Press",
number = "2",

}

TY - JOUR

T1 - Regulation of the p21(Sdi1/Cip1/Waf1) DNA synthesis inhibitor in senescent human diploid fibroblasts

AU - Robetorye, Ryan S.

AU - Smith, James R.

PY - 1996/6

Y1 - 1996/6

N2 - A large body of evidence has demonstrated that normal human fibroblasts have a limited division potential in culture and underwent senescence, a process whereby cells became arrested in the G 1 phase of the cell cycle and overexpressed a DNA synthesis inhibitor(s). Cyclin-dependent kinase two (Cdk2) is required for the promotion of the G 1-to-S phase transition in human cells. Senescent fibroblasts contain intact cyclin-Cdk2 complexes but cannot induce Cdk2 protein kinase activity in response to mitogen stimulation. Recently, we cloned p21(Sdi1), a potent inhibitor of DNA synthesis and Cdk2 kinase activity, from a senescent cell cDNA library and demonstrated that it was expressed at significantly higher levels in senescent cells than actively proliferating cells. In contrast to actively dividing cells, mitogen-stimulated senescent cells do not down-regulate the expression of p21(Sdi1) and do not express late G 1 phase gene products that are required for entry into S phase. We suggest that the inability of mitogen-stimulated senescent cells to down-regulate p21(Sdi1) levels contributes to the resulting lack of late G 1 gene expression and failure to traverse the G 1/S phase boundary.

AB - A large body of evidence has demonstrated that normal human fibroblasts have a limited division potential in culture and underwent senescence, a process whereby cells became arrested in the G 1 phase of the cell cycle and overexpressed a DNA synthesis inhibitor(s). Cyclin-dependent kinase two (Cdk2) is required for the promotion of the G 1-to-S phase transition in human cells. Senescent fibroblasts contain intact cyclin-Cdk2 complexes but cannot induce Cdk2 protein kinase activity in response to mitogen stimulation. Recently, we cloned p21(Sdi1), a potent inhibitor of DNA synthesis and Cdk2 kinase activity, from a senescent cell cDNA library and demonstrated that it was expressed at significantly higher levels in senescent cells than actively proliferating cells. In contrast to actively dividing cells, mitogen-stimulated senescent cells do not down-regulate the expression of p21(Sdi1) and do not express late G 1 phase gene products that are required for entry into S phase. We suggest that the inability of mitogen-stimulated senescent cells to down-regulate p21(Sdi1) levels contributes to the resulting lack of late G 1 gene expression and failure to traverse the G 1/S phase boundary.

KW - Cdk inhibitor

KW - Cdk2

KW - cell cycle

KW - DNA synthesis

KW - p21(Sdi1)

UR - http://www.scopus.com/inward/record.url?scp=0029740819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029740819&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0029740819

VL - 15

SP - 315

EP - 329

JO - Canadian Journal on Aging/La Revue canadienne du vieillissment/Canadian Public Policy/Analyse de Politiques

JF - Canadian Journal on Aging/La Revue canadienne du vieillissment/Canadian Public Policy/Analyse de Politiques

SN - 0714-9808

IS - 2

ER -