Wild-type p53 modulates apoptosis of normal, IL-3 deprived, hematopoietic cells.
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 (IL-3 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 degrees 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.
Blandino
G
G
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, C.R.S., Rome, Italy.
Scardigli
R
R
Rizzo
M G
MG
Crescenzi
M
M
Soddu
S
S
Sacchi
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle; D002455:Cell Division; D004249:DNA Damage; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000502:physiology*; D051379:Mice; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D007377:Interleukin-3; D016159:Tumor Suppressor Protein p53