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 w ith an early step in apoptotic signaling. In a search for E2A-HLF-responsiv e genes, we identified a zinc finger transcription factor, SLUG, whose prod uct belongs to the Snail family of developmental regulatory proteins. Impor tantly, 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. Consiste nt with the postulated role of CES-1 as an antiapoptotic transcription fact or, SLUG was nearly as active as Bcl-2 or Bcl-x(L) in promoting the surviva l of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclud e 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 dea th.