Expression of p53 in differentiation and apoptosis and its deregulation in tumor cell.
The observation that wild type p53 may induce cells to undergo either apoptosis or differentiation raises the question of whether these two events share similar p53-dependent pathways. To evaluate the interrelationship between these two p53-dependent processes, our study focused on the human HL-60, a pro-myelocytic p53 non-producer cell line in which p53 expression was introduced and the induction of apoptosis and differentiation was followed under controlled conditions. p53 expression was induced in the HL-60 cell line by infection with the recombinant wild type p53 (p53WT) vaccinia virus. Viral infection gave rise to cells expressing various levels of wild type p53 protein. High levels of p53 protein induced cells to undergo rapid apoptosis, whereas lower levels of p53 protein induced cells to undergo cell differentiation at a more moderate rate of kinetics. These results suggest that p53 protein levels may determine whether a given cell should prefer one pathway over the other to exit the cell cycle.
Rotter
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Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. LCROTTER@WEIZMANN
Ronen
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D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D018922:HL-60 Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014616:Vaccinia virus
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53