WT1: what has the last decade told us?

Bioessays. 1999 Mar;21(3):191-202. doi: 10.1002/(SICI)1521-1878(199903)21:3<191::AID-BIES3>3.0.CO;2-8.

Abstract

When positionally cloned in late 1989, it was anticipated that mutations within the Wilms' tumour suppressor gene (WT1) would prove responsible for this common solid kidney cancer of childhood. Characterisation of the WT1 expression pattern and of the structure of the encoded protein isoforms and their mode of action has now spanned almost a decade. WT1 proteins act as nucleic acid-binding zinc finger-containing transcription factors involved in both transactivation and repression. These activities are facilitated and constrained by interactions with other proteins. Expression analyses and knockout mice indicate that WT1 protein plays a critical role in normal kidney and gonad development. Specific constitutional WT1 mutations results in several urogenital anomaly syndromes. While only 10% of sporadic Wilms' tumours do display WT1 mutation, WT1 is mutated in other cancers, including acute myeloid leukaemia. Much is still to be determined in WT1 biology. The next decade will see at least three streams of attention. The first two, elucidation of the role of WT1 in RNA metabolism and the characterisation of further protein partners, may together explain the distinct tissue-specific functions of WT1. Finally, further research into the role of WT1 in haematopoiesis will improve our understanding of WT1 in leukaemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Genes, Wilms Tumor*
  • Genotype
  • Humans
  • Kidney / embryology
  • Mice
  • Phenotype
  • RNA / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology*
  • Syndrome
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • WT1 Proteins
  • Wilms Tumor
  • Zinc Fingers*

Substances

  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • Transcription Factors
  • WT1 Proteins
  • RNA
  • DNA