Transcriptional regulation by p53 and p73.
The tumor suppressor p53 exerts its effect through transactivation of a wide variety of genes leading to outcomes such as cell cycle arrest or apoptosis. Both p53 protein levels and modification status are thought to play a role in its ability to discriminate between different target genes and, thereby, cell fate. Here, we have determined the contribution of p53 levels to promoter selectivity when ectopically expressed in H1299 cells. Interestingly, p53AIP1, a pro-apoptotic p53 target gene, requires a significantly higher threshold level of p53 for its activation than p21WAF1, a cell cycle arrest gene. We also found that whereas exogenous p73 exhibits similar transcriptional activity to p53 in H1299 cells, the endogenous p73 that accumulates upon DNA damage in HCT116 cells is unable to compensate for p53 function. Quantification of protein expression levels revealed that the basal expression of TAp73 in HCT116 cells is very low and, even after induction by DNA damage, it accumulates to levels that are lower than basal uninduced levels of p53. These results might partially explain why, unlike p53, p73 does not function as a major tumor suppressor.
Lokshin
M
M
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Tanaka
T
T
Prives
C
C
D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C414742:P53AIP1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins