Induction of IW32 erythroleukemia cell differentiation by p53 is dependent on protein tyrosine phosphatase.
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 beta-globin and the erythroid-specific delta-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 PTPbeta2 and PTPepsilon could be observed by wildtype 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.
National Yang-Ming University, Shih-Pai, Taipei, Taiwan.
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Wang
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D016193:G1 Phase; D015973:Gene Expression Regulation, Leukemic; D016158:Genes, p53; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D005914:Globins; D000624:5-Aminolevulinate Synthetase; D017027:Protein Tyrosine Phosphatases; C098067:Ptpre protein, mouse; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4