title: Structural basis of multimer-mediated mayhem.
abstract: Oligomerization of AML1-ETO contributes to leukemogenesis through obscure mechanisms. In this issue of Cancer Cell, Bushweller and colleagues show the crystal structure of the ETO NHR2 domain to be a tetramer. Tetramer formation is important for maturation arrest and self-renewal, and gene expression is altered in the absence of self-association. Loss of oligomer formation disrupts interactions between AML1-ETO and members of the ETO corepressor family, but not other corepressor molecules posited to be important for leukemogenesis. The findings clarify the role of oligomer formation in AML1-ETO function and suggest a possible therapeutic strategy of targeting ETO-corepressor interactions.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Kajal V
authors.initials: KV
authors.lastname: Sitwala
authors.forename: Jay L
authors.initials: JL
authors.lastname: Hess
mesh_terms: D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D000075142:RUNX1 Translocation Partner 1 Protein
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