Abstract
The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription factor, SLUG was nearly as active as Bcl-2 or Bcl-xL in promoting the survival of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclude that SLUG is an evolutionarily conserved transcriptional repressor whose activation by E2A-HLF promotes the aberrant survival and eventual malignant transformation of mammalian pro-B cells otherwise slated for apoptotic death.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Base Sequence
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Basic-Leucine Zipper Transcription Factors
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Binding Sites
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Cell Survival
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Cell Transformation, Neoplastic / genetics*
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Consensus Sequence
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation, Neoplastic*
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Humans
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Leukemia, B-Cell / genetics*
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Leukemia, B-Cell / metabolism
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Mice
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Models, Genetic
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Multigene Family
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Oncogene Proteins, Fusion / metabolism*
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Protein Binding
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Recombinant Proteins / metabolism
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Snail Family Transcription Factors
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Tissue Distribution
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
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Zinc Fingers*
Substances
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Basic-Leucine Zipper Transcription Factors
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DNA-Binding Proteins
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E2a-Hlf fusion protein, human
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E2a-Hlf fusion protein, mouse
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Oncogene Proteins, Fusion
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Recombinant Proteins
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SNAI1 protein, human
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Snai2 protein, mouse
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Snail Family Transcription Factors
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Transcription Factors