Cell type-specific regulation of calmodulin 2 expression by mutant p53

K X Knaup1, K Roemer

  • 1Department of Virology, University of Saarland Medical School, Bldg. 47, 66421 Homburg/Saar, Germany. karl.knaup@uniklinik-saarland.de

FEBS Letters
|July 1, 2004
PubMed

Insights

Oncogenic mutant p53 (175H) specifically stimulates calmodulin 2 gene expression in fibroblasts. This requires promoter sequences and the mutant p53 transactivation domain, but not direct binding.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Mutant p53 proteins can acquire oncogenic functions.
  • Understanding gene expression changes induced by mutant p53 is crucial for cancer therapy.

Purpose of the Study:

  • To identify genes upregulated by oncogenic mutant p53 (175H).
  • To investigate the mechanism of mutant p53-mediated gene stimulation.

Main Methods:

  • Microarray analysis and PCR-select subtractive hybridization were used to profile gene expression.
  • Human wild-type p53-negative immortal 041 fibroblasts were stably infected to express mutant p53 175H.
  • Reporter assays and in vitro binding assays were employed to study promoter activity and protein-DNA interactions.

Main Results:

  • Mutant p53 175H induced limited gene expression changes compared to wild-type p53.
  • Calmodulin 2 (CaM 2) gene expression was specifically stimulated by mutant p53 175H in 041 cells.
  • CaM 2 promoter stimulation by 175H required its 5' untranslated sequences and transactivation domain integrity.
  • Direct in vitro binding of 175H to the 5' untranslated region was not detected.

Conclusions:

  • Oncogenic mutant p53 175H can specifically induce calmodulin 2 gene expression.
  • The mechanism involves promoter regulatory elements and the mutant p53 transactivation domain, suggesting indirect DNA interaction.
  • These findings contribute to understanding the transcriptional targets and mechanisms of oncogenic mutant p53.

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