The tetramer structure of the Nervy homology two domain, NHR2, is critical for AM1/ETO's activity

被引：108

作者：

Liu, YZ

Cheney, MD

Gaudet, JJ

Chruszcz, M

Lukasik, SM

Sugiyama, D

Lary, J

Cole, J

Dauter, Z

Minor, W

Speck, NA ^{[1
]}

Bushweller, JH

机构：

[1] Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA

[2] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA

[3] Univ Virginia, Dept Chem, Charlottesville, VA 22906 USA

[4] Univ Connecticut, Natl Analyt Ultracentifrugat Facil, Storrs, CT 06269 USA

[5] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA

[6] Brookhaven Natl Lab, Natl Canc Inst, Macromol Crystallog Lab, Upton, NY 11973 USA

来源：

CANCER CELL | 2006年 / 9卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2006.03.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 oligornerization 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.

引用

页码：249 / 260

页数：12

共 66 条

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