Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Wilms' tumor suppressor gene wt1 encodes a zinc finger-containing protein that binds to the same DNA sequence as Egr-1, a mitogen-inducible immediate-early gene product that activates transcription. In this study, we investigated whether the human insulin-like growth factor-II (IGF-II) P4 promoter might be a target for transcriptional repression mediated by WT1. Using constructs of the IGF-II P4 promoter linked to the chloramphenicol acetyltransferase gene, we have demonstrated that the WT1 protein represses expression of the IGF-II gene through a GCGGGGGAG response element spanning nucleotides -87 to -65 of the IGF-II P4 promoter. Conversely, we have shown that the Egr-1 activates transcription of the IGF-II gene through the same response element. WT1 and Egr-1 proteins interact directly with the WT1/Egr-1 response element of the IGF-II promoter 4 in gel mobility-shift assays. These findings demonstrate the importance of the WT1/Egr-1 consensus element for the expression of the IGF-II gene in response to positive or negative transcription signals.
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PMID:Transcriptional repression of human insulin-like growth factor-II P4 promoter by Wilms' tumor suppressor WT1. 863 46

Midkine (MK) is a heparin-binding growth factor which is strongly expressed during the midgestation period of mouse embryogenesis. Wilms' tumor is an embryonal kidney malignancy in infants, and WT1 has been identified as its tumor suppressor gene. The high expression level of MK in all Wilms' tumor specimens so far examined and the presence of two WT1 elements (5'-GCGGGGGCG-3') in the human MK promoter region led us to examine the possible role of the WT1 gene product in the regulation of MK gene expression. A gel shift assay verified the complex formation between the WT1 gene product and WT1 consensus sequence of MK gene. DNase1 footprint analysis also demonstrated that the downstream WT1 element was protected from DNase1 cleavage by the addition of the WT1 protein. The human MK promoter fused with the chloramphenicol acetyltransferase gene (phMK2.3kCAT) was co-transfected with an effector plasmid containing the WT1 gene into several cell lines. Transient transfection assays showed suppression of the MK promoter by WT1 co-transfection in recipient cells; deletion of the WT1 binding site abolished the suppression. The evidence reported in this study indicates that MK gene is a newly identified WT1 target gene.
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PMID:Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1). 895 Sep 87