TY - JOUR
T1 - The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity
AU - Liu, Yizhou
AU - Cheney, Matthew D.
AU - Gaudet, Justin J.
AU - Chruszcz, Maksymilian
AU - Lukasik, Stephen M.
AU - Sugiyama, Daisuke
AU - Lary, Jeff
AU - Cole, James
AU - Dauter, Zbyszek
AU - Minor, Wladek
AU - Speck, Nancy A.
AU - Bushweller, John H.
N1 - Funding Information:
We thank Warren Pear for the MigR1 vector, Scott Hiebert for the cDNAs, and Bruce Hug for his helpful advice. We also thank Harry Higgs for help with the SEC experiments and Jason Moore for statistical support. RO1 CA108056 (J.H.B. and N.A.S.) supported this work. M.D.C. is supported by T32 GM08704, and J.J.G. is supported by T32 AR07576. Flow cytometry was done in The Herbert C. Englert Cell Analysis Laboratory, established by a grant from the Fannie E. Rippel Foundation and supported in part by the Core Grant of the Norris Cotton Cancer Center (CA 23108).
PY - 2006/4
Y1 - 2006/4
N2 - 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 oligomerization 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 α-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.
AB - 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 oligomerization 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 α-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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U2 - 10.1016/j.ccr.2006.03.012
DO - 10.1016/j.ccr.2006.03.012
M3 - Article
C2 - 16616331
AN - SCOPUS:33645778328
SN - 1535-6108
VL - 9
SP - 249
EP - 260
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -
