p53-mediated differentiation of the erythroleukemia cell line K562.
The tumor suppressor gene p53 can mediate both apoptosis and cell cycle arrest. In addition, p53 also influences differentiation. To further characterize the differentiation inducing properties of p53, we overexpressed a temperature-inducible p53 mutant (ptsp53Val135) in the erythroleukemia cell line K562. The results show that wild-type p53 and hemin synergistically induce erythroid differentiation of K562 cells, indicating that p53 plays a role in the molecular regulation of differentiation. However, wild-type p53 did not affect phorbol 12-myristate 13-acetate-dependent appearance of the megakaryocyte-related cell surface antigens CD9 and CD61, suggesting that p53 does not generally affect phenotypic modulation. The cyclin-dependent kinase inhibitor p21, a transcriptional target of p53, halts the cell cycle in G1 and has also been implicated in the regulation of differentiation and apoptosis. However, transiently overexpressed p21 did neither induce differentiation nor affect the cell cycle distribution or viability of K562 cells, suggesting that targets downstream of p53 other than p21 are critical for the p53-mediated differentiation response.
Department of Hematology, Lund University, Sweden. Kristina.Chylicki@hematologi.lu.se
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Chylicki
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Ehinger
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Svedberg
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Bergh
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Olsson
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Gullberg
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001560:Benzidines / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D016923:Cell Death; D002454:Cell Differentiation; D002469:Cell Separation; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005822:Genetic Vectors; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3; D020014:K562 Cells; D008562:Membrane Glycoproteins; D051379:Mice; D016296:Mutagenesis; D010641:Phenotype; D010766:Phosphorylation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011233:Precipitin Tests; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D060245:Tetraspanin 29; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D015703:Antigens, CD; D001560:Benzidines; C554869:CD9 protein, human; C493956:CDKN1A protein, human; C554870:Cd9 protein, mouse; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D006454:Hemoglobins; D039661:Integrin beta3; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D060245:Tetraspanin 29; D016159:Tumor Suppressor Protein p53; C029876:benzidine; D006427:Hemin; D013755:Tetradecanoylphorbol Acetate