Novel cell-specific and dominant negative anti-apoptotic roles of p73 in transformed leukemia cells.
Although extensive homology exists between related genes p53 and p73, recent data suggest that the family members have divergent roles. We demonstrate that the differential regulatory roles of p53 family member p73 are highly cell-context and promoter-specific. Full-length p73 expressed in the transformed leukemia cell line Jurkat behaves as a specific dominant negative transcriptional repressor of the cell cycle inhibitor gene p21 and blocks p53-mediated apoptosis. These findings provide evidence for a new mechanism in oncogenesis through which the functional properties of p73 can be altered in an inheritable and cell-specific fashion independent of transcriptional coding.
Freebern
Wendy J
WJ
Laboratory of Receptor Biology and Gene Expression and Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Smith
James L
JL
Chaudhry
Sohail S
SS
Haggerty
Cynthia M
CM
Gardner
Kevin
K
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D005799:Genes, Dominant; D016147:Genes, Tumor Suppressor; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004247:DNA; D008156:Luciferases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases