AML1-ETO decreases ETO-2 (MTG16) interactions with nuclear receptor corepressor, an effect that impairs granulocyte differentiation

Cancer Research
Vinzon IbañezYogen Saunthararajah

Abstract

The t(8;21) chromosome abnormality in acute myeloid leukemia targets the AML1 and ETO genes to produce the leukemia fusion protein AML1-ETO. Another member of the ETO family, ETO-2/MTG16, is highly expressed in murine and human hematopoietic cells, bears >75% homology to ETO, and like ETO, contains a conserved MYND domain that interacts with the nuclear receptor corepressor (N-CoR). AML1-ETO prevents granulocyte but not macrophage differentiation of murine 32Dcl3 granulocyte/macrophage progenitors. One possible mechanism is recruitment of N-CoR to aberrantly repress AML1 target genes. We wished to examine another mechanism by which AML1-ETO might impair granulocyte differentiation. We demonstrate that AML1-ETO decreases interactions between ETO-2 and N-CoR. Furthermore, overexpression of ETO-2 relieves AML1-ETO-induced granulocyte differentiation arrest. This suggests that decreased interactions between ETO-2 and N-CoR may contribute to granulocyte differentiation impairment. The MYND domain coimmunoprecipitates with N-CoR and inhibits interactions between ETO-2 and N-CoR, presumably by occupying the ETO-2 binding site on N-CoR. This inhibition of ETO-2 interactions with N-CoR is specific because the MYND domain does not inhibi...Continue Reading

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Citations

Apr 27, 2011·Blood·Zhenbo HuYogen Saunthararajah
Aug 18, 2005·International Journal of Hematology·Tetsuya YamagataKinuko Mitani
Feb 22, 2012·European Journal of Medicinal Chemistry·Maria ChatzopoulouAsterios S Tsiftsoglou
Mar 25, 2009·Pharmacology & Therapeutics·Asterios S TsiftsoglouStefanos A Tsiftsoglou
Jan 29, 2005·Experimental Hematology·Sofia Rondin LindbergInge Olsson
Jun 2, 2011·Journal of Biomedicine & Biotechnology·Håkon ReikvamØystein Bruserud
Jan 24, 2018·Stem Cells International·Nickolas SteinauerJinsong Zhang
Feb 4, 2021·Experimental Hematology & Oncology·Daniel T JohnsonDong-Er Zhang

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