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Cell Differentiation and p53

Induction of IW32 erythroleukemia cell differentiation by p53 is dependent on protein tyrosine phosphatase

Abstract

The biological activity of p53 in IW32 erythroleukemia cells was investigated. IW32 cells had no detectable levels of p53 mRNA and protein expression. By transfecting a temperature- sensitive mutant p53 cDNA, tsp53val135, into the cells, we have established several clones stably expressing the mutant p53 allele. At permissive temperature, these p53 transfectants were arrested in G1 phase and underwent apoptosis. Moreover, differentiation along the erythroid pathway was observed as evidenced by increased benzidine staining and mRNA expression of β-globin and the erythroid-specific δ-aminolevulinic acid synthase (ALAS-E). Treatment of cells with protein tyrosine phosphatase inhibitor vanadate blocked the p53-induced differentiation, but not that of cell death or growth arrest. Increased protein tyrosine phosphatase activity as well as mRNA levels of PTPβ2 and PTPε could be observed by wild-type p53 overexpression. These results indicate that p53 induced multiple phenotypic consequences through separate signal pathways in IW32 erythroleukemia cells, and protein tyrosine phosphatase is required for the induced differentiation.

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Acknowledgements

We thank Dr M Oren (Weizmann Institute, Israel) for kindly providing us with the tsp53val135 cDNA. This work was supported by Grants NSC 88-2316-B010-022-M46 and NSC 89–2316-B010-017-M16 from National Science Council, Republic of China.

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Tang, PP., Wang, FF. Induction of IW32 erythroleukemia cell differentiation by p53 is dependent on protein tyrosine phosphatase. Leukemia 14, 1292–1300 (2000). https://doi.org/10.1038/sj.leu.2401823

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