The Predominant WT1 Isoform (+KTS) Encodes a DNA-binding Protein Targeting the Planar Cell Polarity Gene Scribble in Renal Podocytes

Overview

Journal Mol Cancer Res

Specialty Cell Biology

Date 2010 Jun 24

PMID 20571064

Citations 8

Authors

Julie Wells

Miguel N Rivera

Woo Jae Kim

Kristen Starbuck

Daniel A Haber

Affiliations

Soon will be listed here.

Abstract

WT1 encodes a tumor suppressor first identified by its inactivation in Wilms' Tumor. Although one WT1 splicing variant encodes a well-characterized zinc finger transcription factor, little is known about the function of the most prevalent WT1 isoform, whose DNA binding domain is disrupted by a three-amino acid (KTS) insertion. Using cells that conditionally express WT1(+KTS), we undertook a genome-wide chromatin immunoprecipitation and cloning analysis to identify candidate WT1(+KTS)-regulated promoters. We identified the planar cell polarity gene Scribble (SCRB) as the first WT1(+KTS) target gene in podocytes of the kidney. WT1 and SCRB expression patterns overlap precisely in developing renal glomeruli of mice, and WT1(+KTS) binds to a 33-nucleotide region within the Scribble promoter in mouse and human cell lines and kidneys. Together, our results support a role for the predominant WT1(+KTS) isoform in transcriptional regulation and suggest a link between the WT1-dependent tumor suppressor pathway and a key component of the planar cell polarity pathway.

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