p53 expression in K562 cells is associated with caspase-mediated cleavage of c-ABL and BCR-ABL protein kinases.

The chimaeric BCR-ABL oncoprotein is the molecular hallmark of chronic myeloid leukaemia (CML). Expression of Bcr-Abl has been associated with arrested differentiation as well as resistance to apoptosis. The downstream pathway involved in apoptosis resistance has been extensively studied, whereas the role of Bcr-Abl in cell differentiation is largely unclear. A recent report has shown that Bcr-Abl expression alone is sufficient to increase the number of multipotent and myeloid lineage-committed progenitors in a dose-dependent manner while suppressing the development of committed erythroid progenitors. In accordance with this model, downregulation of c-Abl and Bcr-Abl has been observed during differentiation in different systems, although the mechanism is still largely unknown. To investigate the relationship between erythroid differentiation and c-Abl and Bcr-Abl levels, we induced differentiation in K562 cells using a temperature-inducible p53 mutant (p53Val1335). It was found that p53-induced erythroid differentiation in K562 cells required caspase activity. During this process, caspase-dependent cleavage of c-Abl and Bcr-Abl tyrosine kinases was observed, suggesting a new mechanism for the downregulation of the kinases during erythroid differentiation.