Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo

Akira Inoue, Markus G. Seidel, Wenshu Wu, Shintaro Kamizono, Adolfo A. Ferrando, Roderick T. Bronson, Hiromi Iwasaki, Koichi Akashi, Akira Morimoto, Johann K. Hitzler, Tamara I. Pestina, Carl W. Jackson, Ryuhei Tanaka, Miriam J. Chong, Peter J. McKinnon, Takeshi Inukai, Gerard C. Grosveld, A. Thomas Look

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146 Citations (Scopus)

Abstract

We show here that a zinc finger transcriptional repressor, Slug, which is aberrantly upregulated by the E2A-HLF oncoprotein in pro-B cell acute leukemia, functions as an antiapoptotic factor in normal hematopoietic progenitor cells. Slug-/- mice were much more radiosensitive than wild-type mice, dying earlier and showing accentuated decreases in peripheral blood cell counts, as well as abundant microhemorrhages and widely disseminated bacterial microabscesses throughout the body. Slug expression was detected in diverse subsets of hematopoietic progenitors, but not in more differentiated B and T lymphoid cells, and there was a significant increase in apoptotic (TUNEL-positive) bone marrow progenitor cells in irradiated Slug-/- mice compared to wild-type controls. These results implicate Slug in a novel survival pathway that protects hematopoietic progenitors from apoptosis after DNA damage.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalCancer Cell
Volume2
Issue number4
DOIs
Publication statusPublished - Oct 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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    Inoue, A., Seidel, M. G., Wu, W., Kamizono, S., Ferrando, A. A., Bronson, R. T., Iwasaki, H., Akashi, K., Morimoto, A., Hitzler, J. K., Pestina, T. I., Jackson, C. W., Tanaka, R., Chong, M. J., McKinnon, P. J., Inukai, T., Grosveld, G. C., & Look, A. T. (2002). Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo. Cancer Cell, 2(4), 279-288. https://doi.org/10.1016/S1535-6108(02)00155-1