Impaired p53 Expression, Function, and Nuclear Localization in Calreticullum-deficient Cells

Nasrin Mesaeli, Clark Phillipson

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The tumor suppressor protein, p53 is a transcription factor that not only activates expression of genes containing the p53 binding site but also can repress the expression of some genes lacking this binding site. Previous studies have shown that overexpression of wild-type p53 leads to apoptosis and cell cycle arrest. DNA damage, such as that caused by UV irradiation, results in p53 stabilization and nuclear localization that subsequently induces apoptosis. Recently, the level of calreticulin (CRT) has been correlated with the rate of apoptosis. Therefore, the aim of this study was to investigate the role of CRT in the regulation of apoptosis via modulating p53 function and expression. Here we show a significant decrease in both basal and DNA damage induced p53 functions in the CRT-deficient cells (crt-/-). This study is the first to demonstrate that CRT function is required for the stability and localization of the p53 protein. By using immuonocytochemical techniques, we showed that observed changes in p53 in the crt-/- cells are due to the nuclear accumulation of Mdm2 (murine double minute gene). These results, lead us to conclude that CRT regulates p53 function by affecting its rate of degradation and nuclear localization.

Original languageEnglish
Pages (from-to)1862-1870
Number of pages9
JournalMolecular Biology of the Cell
Volume15
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

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Calreticulin
Apoptosis
DNA Damage
Binding Sites
Tumor Suppressor Protein p53
Gene Expression
p53 Genes
Cell Cycle Checkpoints
Transcription Factors
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Impaired p53 Expression, Function, and Nuclear Localization in Calreticullum-deficient Cells. / Mesaeli, Nasrin; Phillipson, Clark.

In: Molecular Biology of the Cell, Vol. 15, No. 4, 04.2004, p. 1862-1870.

Research output: Contribution to journalArticle

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