Alteration of p53 conformation and induction of apoptosis in a murine erythroleukemia cell line by dimethylsulfoxide.
Programmed cell death, or apoptosis, may play an important role in the regulation of hematopoiesis. The tumor suppressor protein p53 has been identified as a key regulator of apoptosis in both normal and malignant hematopoietic cells. Modulation of p53 function is of interest, therefore, both in understanding the control of apoptosis and as a potential therapeutic intervention. In this study we describe the effect on murine erythroleukemia cells, transfected with a temperature-sensitive mutant p53, of exposure to the differentiating agent dimethylsulfoxide (DMSO). Rather than terminally differentiating, these cells are induced to undergo apoptosis. Interestingly, exposure to DMSO leads to an alteration of the protein conformation of the p53 mutant to one recognized by a wild-type specific monoclonal antibody. This is accompanied by a translocation of the p53 protein from the cytoplasm to the nucleus. These results suggest that the activity of some mutant p53 proteins can be functionally modified by exogenous compounds.
Ryan
J J
JJ
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0668.
Clarke
M F
MF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009154:Mutation; D011233:Precipitin Tests; D011487:Protein Conformation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D004121:Dimethyl Sulfoxide