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

98 Citations (Scopus)

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
Publication statusPublished - Apr 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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