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The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization.

Publication ,  Journal Article
Goldman, SC; Chen, CY; Lansing, TJ; Gilmer, TM; Kastan, MB
Published in: Am J Pathol
May 1996

Mutations of the p53 tumor suppressor gene are rarely found in neuroblastoma. Though typically a nuclear protein, a number of tumor cell types have recently been reported to exhibit cytoplasmic p53 immunostaining, and it has been suggested that altered cellular localization is another mechanism of inhibiting p53 function. We examined p53 protein expression, localization, and function in neuroblastoma cell lines with wild-type p53 genes. Basal p53 levels were largely confined to the cytoplasmic compartment in these cells. However, after irradiation, p53 protein levels increased predominately in the nucleus. Transcriptional activity of p53 was intact in these cells because "downstream" proteins, p21WAF1 and MDM2, were induced by irradiation. In contrast to a neuroblastoma cell line harboring a mutant p53 gene, the neuroblastoma cells with wild-type protein were associated with an intact G1 arrest after DNA damage. The induced nuclear protein in these neuroblastoma cells also appeared functional as measured by its capacity to bind to a DNA oligomer containing a p53-consensus sequence. We have concluded that although p53 expression in neuroblastoma cells is primarily localized to the cytosol, ionizing radiation induces a functional p53 protein in the nucleus and that this cytoplasmic sequestration of p53 in human neuroblastoma is not a mechanism of inactivating p53 function.

Duke Scholars

Published In

Am J Pathol

ISSN

0002-9440

Publication Date

May 1996

Volume

148

Issue

5

Start / End Page

1381 / 1385

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Signal Transduction
  • Polymerase Chain Reaction
  • Point Mutation
  • Pathology
  • Neuroblastoma
  • Immunohistochemistry
  • Humans
  • Genes, p53
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Goldman, S. C., Chen, C. Y., Lansing, T. J., Gilmer, T. M., & Kastan, M. B. (1996). The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization. Am J Pathol, 148(5), 1381–1385.
Goldman, S. C., C. Y. Chen, T. J. Lansing, T. M. Gilmer, and M. B. Kastan. “The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization.Am J Pathol 148, no. 5 (May 1996): 1381–85.
Goldman SC, Chen CY, Lansing TJ, Gilmer TM, Kastan MB. The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization. Am J Pathol. 1996 May;148(5):1381–5.
Goldman, S. C., et al. “The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization.Am J Pathol, vol. 148, no. 5, May 1996, pp. 1381–85.
Goldman SC, Chen CY, Lansing TJ, Gilmer TM, Kastan MB. The p53 signal transduction pathway is intact in human neuroblastoma despite cytoplasmic localization. Am J Pathol. 1996 May;148(5):1381–1385.
Journal cover image

Published In

Am J Pathol

ISSN

0002-9440

Publication Date

May 1996

Volume

148

Issue

5

Start / End Page

1381 / 1385

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Signal Transduction
  • Polymerase Chain Reaction
  • Point Mutation
  • Pathology
  • Neuroblastoma
  • Immunohistochemistry
  • Humans
  • Genes, p53