A Novel Repressor, par-4, Modulates Transcription and Growth Suppression Functions of the Wilms' Tumor Suppressor WT1

摘要: The tumor suppressor WT1 represses and activates transcription. loss and/or imbalance of the dual transcriptional activity may contribute to Wilms' tumor. In this study, we identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions repressor. contains putative leucine zipper domain is specifically upregulated during cells (S. F. Sells, D. P. Wood, Jr., S. Joshi-Barve, Muthukkumar, R. J. Jacob, A. Crist, Humphreys, V. M. Rangnekar, Cell Growth Differ. 5:457-466, 1994). repeat was shown interact with zinc finger DNA binding WT1. Immunoprecipitation-Western blot (immunoblot) analyses demonstrated in vivo WT1-par-4 interactions. ubiquitously expressed, found both nucleus cytoplasm. Functionally, inhibited transcription activated by WT1, but not related EGR1. Inhibition WT1-mediated dependent on mediates its physical association addition, augmented repression, possibly contributing an additional repression domain. Consistent these results, functioned repressor when brought promoter via heterologous Significantly, par-4, mutant unable rescued growth suppression caused Thus, novel modulates well