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.

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页码：249 / 260

页数：12

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共 66 条

[11] The small oligomerization domain of gephyrin converts MLL to an oncogene [J].

Eguchi, M ;

Eguchi-Ishimae, M ;

Greaves, M .

BLOOD, 2004, 103 (10) :3876-3882

[12] RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation [J].

Elagib, KE ;

Racke, FK ;

Mogass, M ;

Khetawat, R ;

Delehanty, LL ;

Goldfarb, AN .

BLOOD, 2003, 101 (11) :4333-4341

[13] Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs [J].

Fasshauer, D ;

Sutton, RB ;

Brunger, AT ;

Jahn, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15781-15786

[14] MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes [J].

Fukuyama, T ;

Sueoka, E ;

Sugio, Y ;

Otsuka, T ;

Niho, Y ;

Akagi, K ;

Kozu, T .

ONCOGENE, 2001, 20 (43) :6225-6232

[15] The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family [J].

Gamou, T ;

Kitamura, E ;

Hosoda, F ;

Shimizu, K ;

Shinohara, K ;

Hayashi, Y ;

Nagase, T ;

Yokoyama, Y ;

Ohki, M .

BLOOD, 1998, 91 (11) :4028-4037

[16] Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO [J].

Gelmetti, V ;

Zhang, JS ;

Fanelli, M ;

Minucci, S ;

Pelicci, PG ;

Lazar, MA .

MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (12) :7185-7191

[17] Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype [J].

Growney, JD ;

Shigematsu, H ;

Li, Z ;

Lee, BH ;

Adeisperger, J ;

Rowan, R ;

Curley, DP ;

Kutok, JL ;

Akashi, K ;

Williams, IR ;

Speck, NA ;

Gilliland, DG .

BLOOD, 2005, 106 (02) :494-504

[18] A SWITCH BETWEEN 2-STRANDED, 3-STRANDED AND 4-STRANDED COILED COILS IN GCN4 LEUCINE-ZIPPER MUTANTS [J].

HARBURY, PB ;

ZHANG, T ;

KIM, PS ;

ALBER, T .

SCIENCE, 1993, 262 (5138) :1401-1407

[19] Role of co-repressors in transcriptional repression mediated by the t(8;21), t(16;21), t(12;21), and inv(16) fusion proteins [J].

Hiebert, SW ;

Lutterbach, B ;

Amann, J .

CURRENT OPINION IN HEMATOLOGY, 2001, 8 (04) :197-200

[20] Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia [J].

Higuchi, M ;

O'Brien, D ;

Kumaravelu, P ;

Lenny, N ;

Yeoh, EJ ;

Downing, JR .

CANCER CELL, 2002, 1 (01) :63-74

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