E2A-HLF usurps control of evolutionarily conserved survival pathways.
E2A-HLF, the chimeric fusion protein resulting from the leukemogenic translocation t(17;19), appears to employ evolutionarily conserved signaling cascades for its transforming and antiapoptotic functions. These arise from both impairment of normal E2A function and activation of a survival pathway triggered through the HLF bZip DNA binding and dimerization domain. Recent reports identify wild-type E2A as a tumor suppressor in T lymphocytes. Moreover, E2A-HLF has been shown to activate SLUG, a mammalian homologue of the cell death specification protein CES-1 in Caenorhabditis elegans, which appears to regulate an evolutionarily conserved cell survival program. Recently, several key mouse models have been generated, enabling further elucidation of these pathways on a molecular genetic level in vivo. In this review, we discuss the characteristics of both components of the fusion protein with regard to their contribution to the regulation of cell fate and the oncogenic potential of E2A-HLF.
Seidel
M G
MG
Pediatric Oncology Department, Dana-Farber Cancer Institute, 44 Binney Street, M-630, Boston, Massachusetts, MA 02115, USA.
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D000818:Animals; D017209:Apoptosis; D050976:Basic-Leucine Zipper Transcription Factors; D017173:Caenorhabditis elegans; D019070:Cell Lineage; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014157:Transcription Factors; D014178:Translocation, Genetic
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; D014157:Transcription Factors