2kyg: Difference between revisions

Revision as of 12:31, 18 December 2014

Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity

Structural highlights

2kyg is a 3 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PRKAR2A, PKR2, PRKAR2 (Homo sapiens), RUNX1T1, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2 (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

[KAP2_HUMAN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. [MTG8_HUMAN] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.^[5] ^[6]

Publication Abstract from PubMed

AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RIIalpha)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIalpha). Based on this structure, a key residue in AML1-ETO for PKA(RIIalpha) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RIIalpha) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.

Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity.,Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017^[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
↑ Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH. Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity. J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017 doi:10.1016/j.jmb.2010.08.007

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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH. Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity. J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017 doi:10.1016/j.jmb.2010.08.007

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@@ Line 1: / Line 1: @@
-{{STRUCTURE_2kyg|  PDB=2kyg  |  SCENE=  }}
+==Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity==
-===Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity===
+<StructureSection load='2kyg' size='340' side='right' caption='[[2kyg]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
-{{ABSTRACT_PUBMED_20708017}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2kyg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KYG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KYG FirstGlance]. <br>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAR2A, PKR2, PRKAR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), RUNX1T1, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2kyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kyg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kyg RCSB], [http://www.ebi.ac.uk/pdbsum/2kyg PDBsum]</span></td></tr>
+</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]].
+== Function ==
+[[http://www.uniprot.org/uniprot/KAP2_HUMAN KAP2_HUMAN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.<ref>PMID:10973986</ref> <ref>PMID:16803958</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RIIalpha)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIalpha). Based on this structure, a key residue in AML1-ETO for PKA(RIIalpha) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RIIalpha) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.
-==Disease==
+Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity.,Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017<ref>PMID:20708017</ref>
-[[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]].
-==Function==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[http://www.uniprot.org/uniprot/KAP2_HUMAN KAP2_HUMAN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.<ref>PMID:10973986</ref><ref>PMID:16803958</ref>
+</div>
+== References ==
-==About this Structure==
+<references/>
-[[2kyg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KYG OCA].
+__TOC__
+</StructureSection>
-==See Also==
-*[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
-==Reference==
-<ref group="xtra">PMID:020708017</ref><references group="xtra"/><references/>
 [[Category: Homo sapiens]]
-[[Category: Bushweller, J.]]
+[[Category: Bushweller, J]]
-[[Category: Cierpecki, T.]]
+[[Category: Cierpecki, T]]
-[[Category: Corpora, T A.]]
+[[Category: Corpora, T A]]
 [[Category: Homodimer bound to monomer]]
 [[Category: Protein binding]]
 [[Category: Protein/protein]]

2kyg: Difference between revisions

Revision as of 12:31, 18 December 2014

Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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