Repression of the transforming growth factor-beta 1 gene by the Wilms' tumor suppressor WT1 gene product. | Zendy

Bhakta R. Dey | Zendy; Vikas P. Sukhatme | Zendy; Anita B. Roberts | Zendy; Michael B. Sporn | Zendy; Frank J. Rauscher | Zendy; S J Kim | Zendy

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Repression of the transforming growth factor-beta 1 gene by the Wilms' tumor suppressor WT1 gene product.

Author(s) -

Bhakta R. Dey,

Vikas P. Sukhatme,

Anita B. Roberts,

Michael B. Sporn,

Frank J. Rauscher,

S J Kim

Publication year - 1994

Publication title -

molecular endocrinology

Language(s) - English

Resource type - Journals

eISSN - 1944-9917

pISSN - 0888-8809

DOI - 10.1210/mend.8.5.8058069

Subject(s) - biology , microbiology and biotechnology , repressor , response element , promoter , gene product , transcription (linguistics) , regulation of gene expression , gene , transcription factor , gene expression , cancer research , genetics , linguistics , philosophy

The Wilms' tumor suppressor gene (WT1) encodes a zinc finger DNA binding protein which functions as a transcriptional repressor. In this study we investigated whether the human transforming growth factor-beta 1 (TGF-beta 1) gene might be a target for transcriptional repression mediated by WT1. Using constructs of the TGF-beta 1 promoter linked to the chloramphenicol acetyl transferase gene, we have demonstrated that the WT1 protein represses expression of the TGF-beta 1 gene through a CGGC response element spanning nucleotides -111 to -119 of the TGF-beta 1 promoter. We have also shown in a cotransfection assay that Egr-1, an immediate early growth response gene, activates transcription of the TGF-beta 1 gene through the same response element and that WT1 represses both the basal and Egr-1-induced TGF-beta 1 promoter activity in monkey kidney CV-1 cells. Moreover, WT1 and Egr-1 proteins interact directly with the WT1/Egr-1 response element of the TGF-beta 1 promoter in gel mobility shift assays. These findings provide further definition of transcriptional control of the TGF-beta 1 gene by showing that the WT1 gene product suppresses TGF-beta 1 transcription and that the WT1/Egr-1 consensus element of the human TGF-beta 1 promoter plays a critical role in this repression.

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