Journal ArticleDOI
Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence
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TLDR
Results suggest that the WTL protein may act at the DNA binding site of a growth factor-inducible gene and that loss of DNA-binding activity contributes to the tumorigenic process.Abstract:
The Wilms' tumor locus (WTL) at 11p13 contains a gene that encodes a zinc finger-containing protein that has characteristics of a DNA-binding protein. However, binding of this protein to DNA in a sequence-specific manner has not been demonstrated. A synthetic gene was constructed that contained the zinc finger region, and the protein was expressed in Escherichia coli. The recombinant protein was used to identify a specific DNA binding site from a pool of degenerate oligonucleotides. The binding sites obtained were similar to the sequence recognized by the early growth response-1 (EGR-1) gene product, a zinc finger-containing protein that is induced by mitogenic stimuli. A mutation in the zinc finger region of the protein originally identified in a Wilms' tumor patient abolished its DNA-binding activity. These results suggest that the WTL protein may act at the DNA binding site of a growth factor-inducible gene and that loss of DNA-binding activity contributes to the tumorigenic process.read more
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WT-1 is required for early kidney development
Jordan A. Kreidberg,Hannu Sariola,Janet M. Loring,Masahiro Maeda,Jerry Pelletier,David E. Housman,Rudolf Jaenisch +6 more
TL;DR: A mutation into the murine WT-1 tumor suppressor gene by gene targeting in embryonic stem cells resulted in embryonic lethality in homozygotes, and examination of mutant embryos revealed a failure of kidney and gonad development.
Journal ArticleDOI
Tumor suppressor genes.
TL;DR: Oncogenes are yielding their place at center stage to a second group of actors, the tumor suppressor genes, which promise to teach us equally important lessons about the molecular mechanisms of cancer pathogenesis.
Journal ArticleDOI
Compilation of vertebrate-encoded transcription factors.
Steffen Faisst,Silke Meyer +1 more
Journal ArticleDOI
Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome.
Jerry Pelletier,Jerry Pelletier,Wendy Bruening,Clifford E. Kashtan,S. Michael Mauer,J. Carlos Manivel,Jane E. Striegel,Donald C. Houghton,Claudine Junien,Renée Habib,Laurie Fouser,Richard N. Fine,Bernard L. Silverman,Daniel A. Haber,Daniel A. Haber,David E. Housman +15 more
TL;DR: Analysis of coding exons of the Wilms' tumor suppressor gene (WT1) for germline mutations provides evidence of a direct role for WT1 in Denys-Drash syndrome and thus urogenital system development.
Journal ArticleDOI
Transcription factors, normal myeloid development, and leukemia.
TL;DR: In the hematopoietic system, stem cells undergo a process of commitment to multipotential progenitors, which in turn give rise to mature blood cells.
References
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Journal ArticleDOI
Mutation and Cancer: Statistical Study of Retinoblastoma
TL;DR: The hypothesis is developed that retinoblastoma is a cancer caused by two mutational events, in the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells.
Journal ArticleDOI
Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins
Pamela J. Mitchell,Robert Tjian +1 more
TL;DR: This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors in mammalian DNA binding transcription factors.
Journal ArticleDOI
Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus.
Katherine M. Call,Thomas M Glaser,Caryn Y. Ito,Alan Buckler,Jerry Pelletier,Daniel A. Haber,Elise A. Rose,Astrid Kral,Astrid Kral,Herman Yeger,William H. Lewis,Carol Jones,David E. Housman +12 more
TL;DR: The genetic localization of this gene, its tissue-specific expression, and the function predicted from its sequence lead us to suggest that it represents the 11p13 Wilms' tumor gene.