Regulation of gene expression by WT1 in development and tumorigenesis

Int J Hematol. 2002 Aug;76(2):110-6. doi: 10.1007/BF02982572.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Neoplastic*
  • Hematopoiesis
  • Humans
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • WT1 Proteins / genetics
  • WT1 Proteins / physiology*
  • Wilms Tumor / etiology*
  • Wilms Tumor / genetics
  • Wilms Tumor / metabolism


  • Protein Isoforms
  • WT1 Proteins