title: p53 expression in K562 cells is associated with caspase-mediated cleavage of c-ABL and BCR-ABL protein kinases.
abstract: 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.
authors.affiliation: Tumour Biology Laboratory, Department of Biochemistry, University College, Cork, Ireland.
authors.forename: Alessandra M A
authors.initials: AM
authors.lastname: Di Bacco
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Cotter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D020169:Caspases / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D020014:K562 Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C504649:PSIP1 protein, human; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C026742:plastin; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; D020169:Caspases