p53-mediated differentiation of the erythroleukemia cell line K562

The tumor suppressor gene p53 can mediate both apoptosis and cell cycle arr est. In addition, p53 also influences differentiation. To further character ize the differentiation inducing properties of p53, we overexpressed a temp erature-inducible p53 mutant (ptsp53Val135) in the erythroleukemia cell lin e K562. The results show that wild-type p53 and hemin synergistically induc e 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 meg akaryocyte-related cell surface antigens CD9 and CD61, suggesting that p53 does not generally affect phenotypic modulation. The cyclin-dependent kinas e inhibitor p21, a transcriptional target of p53, halts the cell cycle in G (1) and has also been implicated in the regulation of differentiation and a poptosis. However, transiently overexpressed p21 did neither induce differe ntiation 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.