Structure-function analysis of the WT1 tumor supressor gene product

The Wilms' tumor suppressor gene, WT1, encodes a zinc finger protein thought to be involved in transcriptional regulation. It has been shown in a yeast two-hybrid system that wt1 can form homodimers. In this study, random mutations that abrogate this interaction in yeast were generated and characterized as a preliminary means of defining the amino acid residues required for wt1 homodimerization. Five types of mutations were identified: mutations that alter the 5$ prime$ Untranslated Region (UTR), and silent, frameshift, nonsense and missense mutations. Further examination of the position and effect of the frameshift, nonsense and missense mutations suggested the amino terminus, specifically exons 1 and 2, as the region of the protein required for homodimerization. It is hoped that a better understanding of the wt1-wt1 interaction may shed light on the role of this protein in normal kidney development and tumorigenesis