title: The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity.
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 alpha-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.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Liu
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Cheney
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Gaudet
authors.forename: Maksymilian
authors.initials: M
authors.lastname: Chruszcz
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lukasik
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.forename: Jeff
authors.initials: J
authors.lastname: Lary
authors.forename: James
authors.initials: J
authors.lastname: Cole
authors.forename: Zbyszek
authors.initials: Z
authors.lastname: Dauter
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
authors.forename: John H
authors.initials: JH
authors.lastname: Bushweller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D000075142:RUNX1 Translocation Partner 1 Protein; D016415:Sequence Alignment
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein