Chaperonin TRiC/CCT Recognizes Fusion Oncoprotein AML1-ETO through Subunit-Specific Interactions

Soung Hun Roh, Moses Makokha Kasembeli, Jesús G. Galaz-Montoya, Wah Chiu, David Tweardy

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

AML1-ETO is the translational product of a chimeric gene created by the stable chromosome translocation t (8;21)(q22;q22). It causes acute myeloid leukemia (AML) by dysregulating the expression of genes critical for myeloid cell development and differentiation and recently has been reported to bind multiple subunits of the mammalian cytosolic chaperonin TRiC (or CCT), primarily through its DNA binding domain (AML1-175). Through these interactions, TRiC plays an important role in the synthesis, folding, and activity of AML1-ETO. Using single-particle cryo-electron microscopy, we demonstrate here that a folding intermediate of AML1-ETO's DNA-binding domain (AML1-175) forms a stable complex with apo-TRiC. Our structure reveals that AML1-175 associates directly with a specific subset of TRiC subunits in the open conformation.

Original languageEnglish (US)
Pages (from-to)2377-2385
Number of pages9
JournalBiophysical journal
Volume110
Issue number11
DOIs
StatePublished - Jun 7 2016

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Chaperonin Containing TCP-1
Oncogene Proteins
Cryoelectron Microscopy
DNA
Myeloid Cells
Acute Myeloid Leukemia
Cell Differentiation
Chromosomes
Gene Expression
Genes

ASJC Scopus subject areas

  • Biophysics

Cite this

Chaperonin TRiC/CCT Recognizes Fusion Oncoprotein AML1-ETO through Subunit-Specific Interactions. / Roh, Soung Hun; Kasembeli, Moses Makokha; Galaz-Montoya, Jesús G.; Chiu, Wah; Tweardy, David.

In: Biophysical journal, Vol. 110, No. 11, 07.06.2016, p. 2377-2385.

Research output: Contribution to journalArticle

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