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PMID: 12215008 Published · ppublish English Journal Article Review

Regulation of gene expression by WT1 in development and tumorigenesis.

International journal of hematology ·Vol. 76 ·No. 2 ·2002-08-00 ·Pages 110-6

Ellisen LW

Abstract

WT1 encodes a zinc finger transcription factor implicated in normal development and tumorigenesis. Germline mutation or deletion of WT1 results in a spectrum of abnormal kidney development, male-to-female intersex disorders, and predisposition to pediatric nephroblastoma, Wilms tumor. Initially thought to encode a transcriptional repressor, WT1-dependent functions are now more clearly linked to its property as a transcriptional activator of genes involved in renal development and sex determination. WT1 is expressed in 4 isoforms as a result of 2 alternative messenger RNA splicing events, the more significant of which encodes the 3 amino acids lysine, threonine, and serine (KTS) between zinc fingers 3 and 4. Although WT1 isoforms lacking KTS act as sequence-specific DNA binding factors, a large body of evidence now implicates the KTS-containing isoforms in RNA processing. In keeping with distinct biochemical mechanisms for these isoforms, genetic data from humans and mice point to separate but partially overlapping roles for WT1 (+KTS) and (-KTS) during genitourinary development. Recently, a hematopoietic model system has been used to study functional properties of WT1 in vitro. WT1 expression in primary hematopoietic cells leads to stage-specific effects that may be relevant to WT1-mediated tumor suppression.

MeSH Terms
Animals Gene Expression Regulation, Neoplastic Hematopoiesis Humans Protein Isoforms/genetics,physiology WT1 Proteins/genetics,physiology Wilms Tumor/etiology,genetics,metabolism
Chemicals
Protein Isoforms WT1 Proteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Ellisen Leif W
Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA. [email protected]
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Article Info
Journal
International journal of hematology
Abbr.
Int J Hematol
ISSN
0925-5710
DOI
10.1007/BF02982572
Email
[email protected]
Published
2002-08-00
Pages
110-6
Language
English
Region
Japan
NLM ID
9111627
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02982572 View journal details
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