The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity

  • Yizhou Liu
  • , Matthew D. Cheney
  • , Justin J. Gaudet
  • , Maksymilian Chruszcz
  • , Stephen M. Lukasik
  • , Daisuke Sugiyama
  • , Jeff Lary
  • , James Cole
  • , Zbyszek Dauter
  • , Wladek Minor
  • , Nancy A. Speck
  • , John H. Bushweller

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

AML1/ETO is the chimeric protein resulting from the t(8;21) in acute myeloid leukemia. The Nervy homology 2 (NHR2) domain in ETO mediates oligomerization and AML1/ETO's interactions with ETO, MTGR1, and MTG16, and with the corepressor molecules mSin3A and HDAC1 and HDAC3. We solved the NHR2 domain structure and found it to be an α-helical tetramer. We show that oligomerization contributes to AML1/ETO's inhibition of granulocyte differentiation, is essential for its ability to enhance the clonogenic potential of primary mouse bone marrow cells, and affects AML1/ETO's activity on several endogenous genes. Oligomerization is also required for AML1/ETO's interactions with ETO, MTGR1, and MTG16, but not with other corepressor molecules.

Original languageEnglish
Pages (from-to)249-260
Number of pages12
JournalCancer Cell
Volume9
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Keywords

  • DNA
  • HUMDISEASE
  • PROTEINS

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