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Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.

Publication ,  Journal Article
Inaba, T; Inukai, T; Yoshihara, T; Seyschab, H; Ashmun, RA; Canman, CE; Laken, SJ; Kastan, MB; Look, AT
Published in: Nature
August 8, 1996

The E2A-HLF (for hepatic leukaemia factor) fusion gene, formed by action of the t(17;19) (q22;p13) chromosomal translocation, drives the leukaemic transformation of early B-cell precursors, but the mechanism of this activity remains unknown. Here we report that human leukaemia cells carrying the translocation t(17;19) rapidly died by apoptosis when programmed to express a dominant-negative suppressor of the fusion protein E2A-HLF, indicating that the chimaeric oncoprotein probably affects cell survival rather than cell growth. Moreover, when introduced into murine pro-B lymphocytes, the oncogenic E2A-HLF fusion protein reversed both interleukin-3-dependent and p53-mediated apoptosis. The close homology of the basic region/leucine zipper (bZIP) DNA-binding and dimerization domain of HLF to that of the CES-2 cell-death specification protein of Caenorhabditis elegans suggests a model of leukaemogenesis in which E2A-HLF blocks an early step within an evolutionarily conserved cell-death pathway.

Duke Scholars

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

August 8, 1996

Volume

382

Issue

6591

Start / End Page

541 / 544

Location

England

Related Subject Headings

  • Zinc
  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Translocation, Genetic
  • Transcription Factors
  • Oncogene Proteins, Fusion
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Leucine Zippers
 

Citation

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MLA
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Inaba, T., Inukai, T., Yoshihara, T., Seyschab, H., Ashmun, R. A., Canman, C. E., … Look, A. T. (1996). Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. Nature, 382(6591), 541–544. https://doi.org/10.1038/382541a0
Inaba, T., T. Inukai, T. Yoshihara, H. Seyschab, R. A. Ashmun, C. E. Canman, S. J. Laken, M. B. Kastan, and A. T. Look. “Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.Nature 382, no. 6591 (August 8, 1996): 541–44. https://doi.org/10.1038/382541a0.
Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun RA, Canman CE, et al. Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. Nature. 1996 Aug 8;382(6591):541–4.
Inaba, T., et al. “Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.Nature, vol. 382, no. 6591, Aug. 1996, pp. 541–44. Pubmed, doi:10.1038/382541a0.
Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun RA, Canman CE, Laken SJ, Kastan MB, Look AT. Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. Nature. 1996 Aug 8;382(6591):541–544.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

August 8, 1996

Volume

382

Issue

6591

Start / End Page

541 / 544

Location

England

Related Subject Headings

  • Zinc
  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Translocation, Genetic
  • Transcription Factors
  • Oncogene Proteins, Fusion
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Leucine Zippers