Conformational change of p53 protein in growth factor-stimulated human myelogenous leukemia cells.
Frequent point mutations of the p53 tumor suppressor gene have been detected in solid tumors but not in acute myelogenous leukemia (AML). The inactivation of the suppressor function of the p53 protein in AML cells may be achieved through the acquisition of a mutant-like conformation. We provide evidence in this report that the p53 protein in AML cells switches to a mutant-like conformation in response to growth factor stimulation, and we propose that the conformation of p53 protein is one of the molecular mechanisms in determining whether the cells proliferate or enter apoptosis. We also show that wild-type p53 with mutant-like conformation is not equivalent to mutant p53 in their stability, which is consistent with the fact they have very different biological activities in the cells.
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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Deisseroth
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004355:Drug Stability; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D011487:Protein Conformation / Q000187:drug effects; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*
D006133:Growth Substances; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53