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The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.

Publication ,  Journal Article
Canman, CE; Wolff, AC; Chen, CY; Fornace, AJ; Kastan, MB
Published in: Cancer Res
October 1, 1994

The p53 protein is a critical participant in a signal transduction pathway which mediates a G1 cell cycle arrest and apoptotic cell death in mammalian cells after ionizing irradiation. Cells from patients with the cancer-prone, radiation-sensitive disorder, ataxia-telangiectasia (AT), exhibit suboptimal (delayed and/or defective) induction of p53 protein after ionizing radiation with some dependence on dose. Other protein products which participate in this signal transduction pathway, including p21WAF1/CIP1, Gadd45, and Mdm2, are also suboptimally induced in AT cells after ionizing radiation. Induction of p53 is also abnormal in AT cells following treatment with methylmethanesulfonate and bleomycin but appears relatively normal following treatment with UV-C irradiation or the topoisomerase inhibitors, etoposide and camptothecin. These results demonstrate a specific defect in this p53-dependent signal transduction pathway in AT cells. Potential models for this observed specificity of the AT defect as measured by p53 induction include problems with responses to: (a) single-strand, but not double-strand, DNA breaks; or (b) chemically, but not enzymatically, generated DNA ends.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1994

Volume

54

Issue

19

Start / End Page

5054 / 5058

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Oncology & Carcinogenesis
  • Methyl Methanesulfonate
  • Humans
  • G1 Phase
  • DNA Damage
  • Ataxia Telangiectasia
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Canman, C. E., Wolff, A. C., Chen, C. Y., Fornace, A. J., & Kastan, M. B. (1994). The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia. Cancer Res, 54(19), 5054–5058.
Canman, C. E., A. C. Wolff, C. Y. Chen, A. J. Fornace, and M. B. Kastan. “The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.Cancer Res 54, no. 19 (October 1, 1994): 5054–58.
Canman CE, Wolff AC, Chen CY, Fornace AJ, Kastan MB. The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia. Cancer Res. 1994 Oct 1;54(19):5054–8.
Canman, C. E., et al. “The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.Cancer Res, vol. 54, no. 19, Oct. 1994, pp. 5054–58.
Canman CE, Wolff AC, Chen CY, Fornace AJ, Kastan MB. The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia. Cancer Res. 1994 Oct 1;54(19):5054–5058.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1994

Volume

54

Issue

19

Start / End Page

5054 / 5058

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Oncology & Carcinogenesis
  • Methyl Methanesulfonate
  • Humans
  • G1 Phase
  • DNA Damage
  • Ataxia Telangiectasia
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis