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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

Nyckelord

Animals

Antigens, CD/metabolism

Benzidines/metabolism

Blotting, Western

Cell Cycle

Cell Death

Cell Differentiation

Cell Separation

Cyclin-Dependent Kinase Inhibitor p21

Cyclins/metabolism

DNA, Complementary/metabolism

Dose-Response Relationship, Drug

Flow Cytometry

Genetic Vectors

Hemin/metabolism

Hemoglobins/metabolism

Humans

Integrin beta3

K562 Cells

Membrane Glycoproteins

Mice

Mutagenesis

Phenotype

Phosphorylation

Platelet Membrane Glycoproteins/metabolism

Precipitin Tests

Temperature

Tetradecanoylphorbol Acetate/pharmacology

Tetraspanin 29

Time Factors

Transfection

Tumor Suppressor Protein p53/genetics

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)