The role of p53 in the induction of polyploidity of myelomonocytic leukemic M1/2 cells.
p53 was shown to play a central role in the maintenance of genomic integrity. The present experiments suggest that p53 is involved in the control of cell ploidity. Using a p53 non-producer cell line, M1/2, that was reconstituted to express either wild type or mutant p53 protein, by infection with the temperature sensitive (Ts) p53Val135 virus, it was found that both loss of wild type p53 or overexpression of mutant p53, may be associated with the generation of cell polyploidity. Overexpression of mutant p53 protein enhanced the appearance of giant cells that further accumulated following gamma-irradiation. Expression of wild type p53 reduced the level of giant cells which accumulated in the parental M1/2 p53 non-producer cells following gamma-irradiation. This activity of the wild type p53 seems to be mediated by either the reduction in the rate of giant cell generation, as observed in M1/2 derived cell lines expressing low levels of wild type p53 protein or by facilitating their apoptosis, as observed in wild type p53 high-producer cells. The latter conclusion is further supported by the observation that isolated giant cells are directly induced to undergo apoptosis following wild type p53 expression.
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
A
A
Peled
D
D
Schwartz
N B
NB
Elkind
R
R
Wolkowicz
R
R
Li
V
V
Rotter
D000818:Animals; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000378:metabolism; D005720:Gamma Rays; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009154:Mutation; D011003:Ploidies; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53