ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors

Bart Lutterbach, Jennifer J Westendorf, Bryan Linggi, Andrea Patten, Mariko Moniwa, James R. Davie, Khanh D. Huynh, Vivian J. Bardwell, Robert M. Lavinsky, Michael G. Rosenfeld, Christopher Glass, Edward Seto, Scott W. Hiebert

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342 Scopus citations

Abstract

t(8;21) is one of the most frequent translocations associated with acute myeloid leukemia. It produces a chimeric protein, acute myeloid leukemia-1 (AML-1)-eight-twenty-one (ETO), that contains the amino-terminal DNA binding domain of the AML-1 transcriptional regulator fused to nearly all of ETO. Here we demonstrate that ETO interacts with the nuclear receptor corepressor N-CoR, the mSin3 corepressors, and histone deacetylases. Endogenous ETO also cosediments on sucrose gradients with mSin3A, N-CoR, and histone deacetylases, suggesting that it is a component of one or more corepressor complexes. Deletion mutagenesis indicates that ETO interacts with mSin3A independently of its association with N-CoR. Single amino acid mutations that impair the ability of ETO to interact with the central portion of N-CoR affect the ability of the t(8;21) fusion protein to repress transcription. Finally, AML-1/ETO associates with histone deacetylase activity and a histone deacetylase inhibitor impairs the ability of the fusion protein to repress transcription. Thus, t(8;21) fuses a component of a corepressor complex to AML-1 to repress transcription.

Original languageEnglish (US)
Pages (from-to)7176-7184
Number of pages9
JournalMolecular and Cellular Biology
Volume18
Issue number12
StatePublished - Dec 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Lutterbach, B., Westendorf, J. J., Linggi, B., Patten, A., Moniwa, M., Davie, J. R., Huynh, K. D., Bardwell, V. J., Lavinsky, R. M., Rosenfeld, M. G., Glass, C., Seto, E., & Hiebert, S. W. (1998). ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Molecular and Cellular Biology, 18(12), 7176-7184.