p53 activates Fanconi anemia group C gene expression.
The tumor suppressor protein p53 (wtp53) can bind to specific target sequences and activate transcription of genes adjacent to these DNA elements. Two p53 binding sites are present in the gene coding for the Fanconi anemia complementation group C (FAC), one in the promoter region (from -1295 to -1266) and one in the coding region of FAC (from +1828 to +1848). Gel shift experiments show that wtp53 binds to the p53 target sequence in the promoter region of the FAC gene. We have investigated whether binding of p53 to these target sites may affect expression of the FAC gene. Transfection experiments show that overexpression of wtp53 in human diploid fibroblasts and lymphoblasts augments transcription of the FAC gene up to three-fold. The transfection efficacy was approximately 15% for both cell types. The FAC expression activity per transformed cell was stimulated to an estimated level of 18- to 21-fold upon overexpression of p53. The tumor-derived p53 mutants, His175 and His273, that fail to bind DNA showed only a reduced stimulatory activity on FAC transcription. Luciferase assays demonstrated that interaction of p53 with its target site in the FAC promoter does not modulate the promoter activity. We suggest that the p53 binding site contributes to, but may not be an absolute prerequisite for p53-directed transcriptional activation. We conclude that the FAC gene can be added to the list of genes that interact with p53.
Liebetrau
W
W
Department of Human Genetics, University of Wuerzburg, Germany.
Budde
A
A
Savoia
A
A
Grummt
F
F
Hoehn
H
H
D001665:Binding Sites; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53