SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein.
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.
Inukai
T
T
Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Inoue
A
A
Kurosawa
H
H
Goi
K
K
Shinjyo
T
T
Ozawa
K
K
Mao
M
M
Inaba
T
T
Look
A T
AT
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D005810:Multigene Family; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C076554:E2a-Hlf fusion protein, human; C489626:E2a-Hlf fusion protein, mouse; D015514:Oncogene Proteins, Fusion; D011994:Recombinant Proteins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors