Gene regulation by temperature-sensitive p53 mutants: identification of p53 response genes.
The ability of the p53 protein to act as a sequence-specific transcriptional activator suggests that genes induced by p53 may encode critical mediators of p53 tumor suppression. Using a tetracycline-regulated p53 expression system and cDNA library subtraction procedure, we identified several p53-induced gene transcripts in human Saos-2 osteosarcoma cells that are novel on the basis of their size, regulation, and low abundance. Wild-type p53-dependent induction of these transcripts was observed in cells that are growth arrested by p53, as well as in cells that undergo apoptosis upon expression of an inducible wild-type p53 transgene. These results show that p53 activates the expression of numerous response genes and suggest that multiple effectors may play a role in mediating cellular functions of p53.
Buckbinder
L
L
Department of Molecular Genetics and Cell Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08540.
Talbott
R
R
Seizinger
B R
BR
Kley
N
N
D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015723:Gene Library; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism; D012516:Osteosarcoma; D010957:Plasmids; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D013696:Temperature; D013752:Tetracycline / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; D013752:Tetracycline