Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53.
Activating transcription factor 3 (ATF3) is an immediate early response gene that is induced in cells exposed to a variety of stress stimuli. In this report, upon exposure of cells to ultraviolet (UV) or proteasome inhibitor MG132, ATF3 protein was induced more efficiently in cells with intact p53 allele than in those with null mutant p53 allele. In Saos-2 cells harboring the temperature-sensitive mutant p53(Val-138), the expression of ATF3 gene was more significant at permissive temperature of 32.5 degrees C than at non-permissive 37.5 degrees C. Reporter assay of the human ATF3 gene promoter identified two p53-responsive elements at -379 to -370 and -351 to -342 from the transcriptional start site. These elements were capable of conferring p53 responsiveness to a heterologous promoter and specifically bound p53 protein in electrophoretic mobility shift assay. Furthermore, ATF3 gene promoter was more significantly activated by UV in cells with wild p53 allele. These results clearly show that the human ATF3 gene is one of the target genes directly activated by p53 and may suggest a functional link between stress-inducible transcriptional repressor ATF3 and p53.
Zhang
Chun
C
Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, 113-8510, Bunkyo-ku, Tokyo, Japan.
Gao
Choungfeng
C
Kawauchi
Junya
J
Hashimoto
Yoshinori
Y
Tsuchida
Nobuo
N
Kitajima
Shigetaka
S
D051700:Activating Transcription Factor 3; D000483:Alleles; D015153:Blotting, Western; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008957:Models, Genetic; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D051700:Activating Transcription Factor 3; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde