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1wq6

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Revision as of 13:26, 6 January 2015

The tetramer structure of the nervy homolgy two (NHR2) domain of AML1-ETO is critical for AML1-ETO'S activity

Structural highlights

1wq6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	AML1/ETO (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[MTG8_HUMAN] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.^[1] ^[2] ^[3] ^[4] Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:114500].

Function

[MTG8_HUMAN] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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 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.

The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity.,Liu Y, Cheney MD, Gaudet JJ, Chruszcz M, Lukasik SM, Sugiyama D, Lary J, Cole J, Dauter Z, Minor W, Speck NA, Bushweller JH Cancer Cell. 2006 Apr;9(4):249-60. PMID:16616331^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J. 1993 Jul;12(7):2715-21. PMID:8334990
↑ Era T, Asou N, Kunisada T, Yamasaki H, Asou H, Kamada N, Nishikawa S, Yamaguchi K, Takatsuki K. Identification of two transcripts of AML1/ETO-fused gene in t(8;21) leukemic cells and expression of wild-type ETO gene in hematopoietic cells. Genes Chromosomes Cancer. 1995 May;13(1):25-33. PMID:7541640
↑ Kozu T, Miyoshi H, Shimizu K, Maseki N, Kaneko Y, Asou H, Kamada N, Ohki M. Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction. Blood. 1993 Aug 15;82(4):1270-6. PMID:8353289
↑ Nisson PE, Watkins PC, Sacchi N. Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. Cancer Genet Cytogenet. 1992 Oct 15;63(2):81-8. PMID:1423235
↑ Wood JD, Nucifora FC Jr, Duan K, Zhang C, Wang J, Kim Y, Schilling G, Sacchi N, Liu JM, Ross CA. Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription. J Cell Biol. 2000 Sep 4;150(5):939-48. PMID:10973986
↑ Plevin MJ, Zhang J, Guo C, Roeder RG, Ikura M. The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10242-7. Epub 2006 Jun 27. PMID:16803958
↑ Liu Y, Cheney MD, Gaudet JJ, Chruszcz M, Lukasik SM, Sugiyama D, Lary J, Cole J, Dauter Z, Minor W, Speck NA, Bushweller JH. The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity. Cancer Cell. 2006 Apr;9(4):249-60. PMID:16616331 doi:10.1016/j.ccr.2006.03.012

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wq6"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1wq6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WQ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WQ6 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AML1/ETO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AML1/ETO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wq6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wq6 RCSB], [http://www.ebi.ac.uk/pdbsum/1wq6 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wq6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wq6 RCSB], [http://www.ebi.ac.uk/pdbsum/1wq6 PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.<ref>PMID:8334990</ref> <ref>PMID:7541640</ref> <ref>PMID:8353289</ref> <ref>PMID:1423235</ref>   Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bushweller, J H.]]
+[[Category: Bushweller, J H]]
-[[Category: Cheney, M D.]]
+[[Category: Cheney, M D]]
-[[Category: Chruszcz, M.]]
+[[Category: Chruszcz, M]]
-[[Category: Dauter, Z.]]
+[[Category: Dauter, Z]]
-[[Category: Hartman, K L.]]
+[[Category: Hartman, K L]]
-[[Category: Laue, T M.]]
+[[Category: Laue, T M]]
-[[Category: Liu, Y.]]
+[[Category: Liu, Y]]
-[[Category: Lukasik, S M.]]
+[[Category: Lukasik, S M]]
-[[Category: Minor, W.]]
+[[Category: Minor, W]]
-[[Category: Speck, N A.]]
+[[Category: Speck, N A]]
 [[Category: Aml1-eto]]
 [[Category: Eto]]
 [[Category: Nhr2]]
 [[Category: Oncoprotein]]

1wq6

From Proteopedia

Revision as of 13:26, 6 January 2015

The tetramer structure of the nervy homolgy two (NHR2) domain of AML1-ETO is critical for AML1-ETO'S activity

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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