An acute myeloid leukemia gene, AML 1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms

T. Tanaka, K. Tanaka, S. Ogawa, M. Kurokawa, K. Mitani, J. Nishida, Y. Shibata, Y. Yazaki, H. Hirai

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA binding protein. From the AML1 gene, two representative forms of proteins, AML1a and AML1b, are produced by alternative splicing. Both forms have a DNA binding domain but, unlike AML1b, AML1a lacks a putative transcriptional activation domain. Here we demonstrate that overexpressed AML1a totally suppresses granulocytic differentiation and stimulates cell proliferation in 32Dcl3 murine myeloid cells treated with granulocyte colony-stimulating factor. These effects of AML1a were canceled by the concomitant overexpression of AML1b. Such biological phenomena could be explained by our observations that (i) AML1a, which on its own has no effects as a transcriptional regulator, dominantly suppresses transcriptional activation by AML1b, and (ii) AML1a exhibits the higher affinity for DNA binding compared with AML1b. These antagonistic actions could be important in leukemogenesis and/or myeloid cell differentiation because more than half of myelogenous leukemia patients showed an increase in the relative amounts of AML1a.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalEMBO Journal
Volume14
Issue number2
DOIs
Publication statusPublished - 1995 Jan 1
Externally publishedYes

Keywords

  • AML1
  • Alternative splicing
  • Antagonistic action
  • Myeloid differentiation
  • Transcriptional activation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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