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A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.

Publication ,  Journal Article
Kastan, MB; Zhan, Q; el-Deiry, WS; Carrier, F; Jacks, T; Walsh, WV; Plunkett, BS; Vogelstein, B; Fornace, AJ
Published in: Cell
November 13, 1992

Cell cycle checkpoints can enhance cell survival and limit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a G1 checkpoint activated by ionizing radiation (IR) when both wild-type p53 alleles were disrupted. In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was dependent on wild-type p53 function. Wild-type but not mutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

November 13, 1992

Volume

71

Issue

4

Start / End Page

587 / 597

Location

United States

Related Subject Headings

  • Mutagenesis
  • Molecular Sequence Data
  • Mice
  • Humans
  • Genes, p53
  • Gene Expression Regulation
  • Developmental Biology
  • DNA Repair
  • DNA Damage
  • Cloning, Molecular
 

Citation

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Kastan, M. B., Zhan, Q., el-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., … Fornace, A. J. (1992). A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell, 71(4), 587–597. https://doi.org/10.1016/0092-8674(92)90593-2
Kastan, M. B., Q. Zhan, W. S. el-Deiry, F. Carrier, T. Jacks, W. V. Walsh, B. S. Plunkett, B. Vogelstein, and A. J. Fornace. “A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.Cell 71, no. 4 (November 13, 1992): 587–97. https://doi.org/10.1016/0092-8674(92)90593-2.
Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71(4):587–97.
Kastan, M. B., et al. “A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.Cell, vol. 71, no. 4, Nov. 1992, pp. 587–97. Pubmed, doi:10.1016/0092-8674(92)90593-2.
Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71(4):587–597.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

November 13, 1992

Volume

71

Issue

4

Start / End Page

587 / 597

Location

United States

Related Subject Headings

  • Mutagenesis
  • Molecular Sequence Data
  • Mice
  • Humans
  • Genes, p53
  • Gene Expression Regulation
  • Developmental Biology
  • DNA Repair
  • DNA Damage
  • Cloning, Molecular