SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein

Mol Cell. 1999 Sep;4(3):343-52. doi: 10.1016/s1097-2765(00)80336-6.


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

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

MeSH terms

  • Animals
  • Apoptosis
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors
  • Binding Sites
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics*
  • Consensus Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, B-Cell / genetics*
  • Leukemia, B-Cell / metabolism
  • Mice
  • Models, Genetic
  • Multigene Family
  • Oncogene Proteins, Fusion / metabolism*
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Snail Family Transcription Factors
  • Tissue Distribution
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Zinc Fingers*


  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • E2a-Hlf fusion protein, human
  • E2a-Hlf fusion protein, mouse
  • Oncogene Proteins, Fusion
  • Recombinant Proteins
  • SNAI1 protein, human
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors