NDLI: Differential Function of Wilms Tumor Gene WT1 Splice Isoforms in Transcriptional Regulation

Content Provider	Journal of Biological Chemistry (JBC)
Author	Hewitt, Stephen M. Fraizer, Gail C. Wu, Ying-Ji Iii, Frank J. Rauscher Saunders, Grady F. Rauscher, Frank J.
Abstract	The Wilms' tumor gene, WT1, encodes a zinc finger transcription factor that can repress transcription of a number of genes. WT1 mRNA undergoes alternative splicing at two locations, yielding four different mRNA species and protein products. One alternative splice alters the zinc finger region of WT1, resulting in the addition of three amino acids, Lys-Thr-Ser (KTS), between zinc fingers 3 and 4, altering the binding of WT1 to DNA. Here, we show that the WT1 protein with and without the KTS tripeptide can repress transcription from the human full-length WT1 promoter. Repression of transcription by WT1 has been shown to require two WT1 binding sites. We examined WT1 repression of the human minimal WT1 promoter, which contains two potential WT1 binding motifs. WT1 lacking the KTS tripeptide (WT1-KTS) was unable to repress transcription from a minimal WT1 promoter of 104 base pairs, whereas WT1 containing the KTS tripeptide (WT1+KTS) repressed transcription from the minimal promoter. The ability of WT1+KTS to repress transcription where WT1-KTS could not provided a functional assay to define differential WT1 binding motifs based on the presence or the absence of the KTS tripeptides. We present data defining the differential consensus DNA binding motifs for WT1-KTS and WT1+KTS. We demonstrate that WT1 zinc finger 1 plays a role in the differential DNA binding specificity of WT1-KTS and WT1+KTS.
Related Links	http://www.jbc.org/content/271/15/8588.abstract
Ending Page	8592
Starting Page	8588
Page Count	5
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	15
Volume Number	271
DOI	10.1074/jbc.271.15.8588
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	1996-04-12
Access Restriction	Open
Subject Keyword	Nucleic Acids, Protein Synthesis, and Molecular Genetics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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