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Science 31 July 1992:
Vol. 257. no. 5070, pp. 674 - 678
DOI: 10.1126/science.1323141
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Articles

Science, Vol 257, Issue 5070, 674-678
Copyright © 1992 by American Association for the Advancement of Science

articles

Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1

IA Drummond, SL Madden, P Rohwer-Nutter, GI Bell, VP Sukhatme, and FJ Rauscher 3rd

Howard Hughes Medical Institute, University of Chicago, IL 60637.

The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as a transcriptional repressor. The fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in Wilms tumors and may have autocrine effects in tumor progression. The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site. WT1 bound to multiple sites in this region and functioned as a potent repressor of IGF-II transcription in vivo. Maximal repression was dependent on the presence of WT1 binding sites on each side of the transcriptional initiation site. These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney.


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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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Transcriptional Silencer of the Wilms' Tumor Gene WT1 Contains an Alu Repeat.
S. M. Hewitt, G. C. Fraizer, and G. F. Saunders (1995)
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   Abstract »    Full Text »    PDF »
WT1-mediated Transcriptional Activation Is Inhibited by Dominant Negative Mutant Proteins.
J. C. Reddy, J. C. Morris, J. Wang, M. A. English, D. A. Haber, Y. Shi, and J. D. Licht (1995)
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Repression of Pax-2 by WT1 during normal kidney development.
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Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues.
S. Mundlos, J. Pelletier, A. Darveau, M. Bachmann, A. Winterpacht, and B. Zabel (1993)
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