| First Author | Dehbi M | Year | 1998 |
| Journal | Oncogene | Volume | 16 |
| Issue | 16 | Pages | 2033-9 |
| PubMed ID | 9572484 | Mgi Jnum | J:47291 |
| Mgi Id | MGI:1203266 | Doi | 10.1038/sj.onc.1201747 |
| Citation | Dehbi M, et al. (1998) Activation of the wt1 Wilms' tumor suppressor gene by NF-kappaB. Oncogene 16(16):2033-9 |
| abstractText | The Wilm's tumor suppressor gene, wt1, is expressed in a very defined spatial-temporal fashion and plays a key role in development of the urogenital system. Transacting factors governing wt1 expression are poorly defined. The presence of putative kappa-B binding sites within the wt1 gene prompted us to investigate whether members of the NF-kappaB/Rel family of transcription factors are involved in regulating wt1 expression. In transient transfection assays, ectopic expression of p50 and p65 subunits of NF-kappaB stimulated wt1 promoter activity 10-30-fold. Deletion mutagenesis revealed that NF-kappa-B responsiveness is mediated by a short DNA fragment located within promoter proximal sequences of the major transcription start site. Two kappaB-binding sites are present in this region and form specific complexes with purified NF-kappaB proteins, as revealed by electrophoretic mobility gel shift assays. Ectopic expression of p50 and p65 resulted in increased transcription of the endogenous wt1 gene, as revealed by nuclear run-on experiments. Taken together, these results indicate that members of the NF-kappaB/Rel family are important for activating expression of wt1 and reside upstream of the regulatory cascade leading to wt1 activation. |
