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. 1994 Jun 21;91(13):5878–5882. doi: 10.1073/pnas.91.13.5878

c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle.

J J Ryan 1, E Prochownik 1, C A Gottlieb 1, I J Apel 1, R Merino 1, G Nuñez 1, M F Clarke 1
PMCID: PMC44100  PMID: 8016082

Abstract

We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation.

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Selected References

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