Wild-type p53 modulates apoptosis of normal, IL-3 deprived, hematopoietic cells

Giovanni Blandino, Raffaella Scardigli, Maria Giulia Rizzo, Marco Crescenzi, Silvia Soddu, Ada Sacchi

Research output: Contribution to journalArticle

Abstract

Apoptotic cell death is an active process which regulates the maintenance of the hematopoietic homeostasis. It has been reported that wild-type p53 (wt-p53) protein induces apoptosis in leukemia cells. To assess whether p53 is involved in the apoptotic process of normal hematopoietic cells, we introduced the temperature-sensitive p53Val135 mutant into the murine myeloid precursor cell line 32Dcl3. These are diploid, non-tumorigenic cells whose survival and proliferation are dependent upon growth factor supply (IL3 and serum). Overexpression of wt-p53 protein does not affect morphology and proliferation of 32D cells as long as they are maintained in the presence of IL-3. However, after IL-3 withdrawal, wt-p53 overexpression significantly accelerates apoptosis. This phenomenon is IL-3 specific since no differences in death rates induced by serum starvation are found between parental cells and p53-transfectants. When the latter experiments are carried out at 37°C with p53 protein in mutant conformation, an extended survival of 32D cells is observed after IL-3 deprivation, but not after serum withdrawal. Taken together, these results show that wt-p53 actively mediates the apoptosis due to the absence of specific growth factors, such as IL-3, suggesting that p53 might be involved in the response of myeloid precursors to environmental cytokines for the maintenance of the hematopoietic homeostasis.

Original languageEnglish
Pages (from-to)731-737
Number of pages7
JournalOncogene
Volume10
Issue number4
Publication statusPublished - Feb 16 1995

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Keywords

  • Apoptosis
  • IL-3-dependence
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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