The Wilms' tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene.
The Wilms' tumor locus on chromosome 11p13 contains a tumor suppressor gene, wt1, which encodes a DNA binding protein (WT1) with four zinc fingers and a glutamine-proline-rich N terminus and which functions as a repressor of transcription. The platelet-derived growth factor (PDGF) A-chain gene encodes a potent growth factor, which is expressed in high levels in a number of tumor cell lines. We initiated a search for WT1 target genes and now report that WT1 strikingly represses transcription of the PDGF A-chain gene in transient transfection assays and that the WT1 protein interacts directly with a highly G+C-rich region of the PDGF A-chain promoter in gel mobility shift assays. The results suggest that WT1 may function to repress expression of the PDGF A-chain gene and that loss of this or related repressor activities may contribute to the abnormal growth of Wilms' tumors.
Wang
Z Y
ZY
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Madden
S L
SL
Deuel
T F
TF
Rauscher
F J
FJ
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D012097:Repressor Proteins; D025721:WT1 Proteins