CDC2 is down-regulated by ionizing radiation in a p53-dependent manner

Edouard Azzam, Sonia M. De Toledo, Mark J. Pykett, Hatsumi Nagasawa, John B. Little

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The mammalian cellular response to ionizing radiation results in delays in progression through the cell cycle at several checkpoints and includes alterations in the activity of cyclin-dependent kinases. The product of the CDC2 gene is a key kinase involved in cell cycle progression. The signaling events that regulate its expression after exposure to DNA-damaging agents are not known. We show that cdc2 mRNA and protein are down-regulated after irradiation of normal human and mouse fibroblasts with doses as low as 0.5 Gy. This down-regulation is preceded by induction of p53 and p21(Waf1) proteins. In human cells in which p53 was nonfunctional and in p53(-/-) or p21(-/-) mouse embryo fibroblasts, no effect of ionizing radiation on p34(cdc2) expression levels was observed. These findings indicate that CDC2 down-regulation after irradiation is p53-dependent and involves the cyclin- dependent kinase inhibitor p21(Waf1) as a negative factor in the control of CDC2 expression. Correspondence between the delay in initiation of DNA synthesis in irradiated cells and the down-regulation of CDC2 is described.

Original languageEnglish (US)
Pages (from-to)1161-1169
Number of pages9
JournalCell Growth and Differentiation
Volume8
Issue number11
StatePublished - Nov 1 1997
Externally publishedYes

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Ionizing Radiation
Down-Regulation
Cell Cycle
Fibroblasts
CDC2 Protein Kinase
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases
DNA
Phosphotransferases
Embryonic Structures
Messenger RNA
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Azzam, E., De Toledo, S. M., Pykett, M. J., Nagasawa, H., & Little, J. B. (1997). CDC2 is down-regulated by ionizing radiation in a p53-dependent manner. Cell Growth and Differentiation, 8(11), 1161-1169.
Azzam, Edouard ; De Toledo, Sonia M. ; Pykett, Mark J. ; Nagasawa, Hatsumi ; Little, John B. / CDC2 is down-regulated by ionizing radiation in a p53-dependent manner. In: Cell Growth and Differentiation. 1997 ; Vol. 8, No. 11. pp. 1161-1169.
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Azzam, E, De Toledo, SM, Pykett, MJ, Nagasawa, H & Little, JB 1997, 'CDC2 is down-regulated by ionizing radiation in a p53-dependent manner', Cell Growth and Differentiation, vol. 8, no. 11, pp. 1161-1169.

CDC2 is down-regulated by ionizing radiation in a p53-dependent manner. / Azzam, Edouard; De Toledo, Sonia M.; Pykett, Mark J.; Nagasawa, Hatsumi; Little, John B.

In: Cell Growth and Differentiation, Vol. 8, No. 11, 01.11.1997, p. 1161-1169.

Research output: Contribution to journalArticle

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Azzam E, De Toledo SM, Pykett MJ, Nagasawa H, Little JB. CDC2 is down-regulated by ionizing radiation in a p53-dependent manner. Cell Growth and Differentiation. 1997 Nov 1;8(11):1161-1169.