| Structural highlights
2knh is a 2 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: | 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
[MTG8_HUMAN] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.[5] [6] [HTF4_HUMAN] Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3').
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 product of the t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the eTAFH domain, which is homologous to several TATA binding protein-associated factors (TAFs) and interacts with E proteins (E2A and HEB). It has been proposed that AML1-ETO-mediated silencing of E protein function might be important for t(8;21) leukemogenesis. Here, we determined the solution structure of a complex between the AML1-ETO eTAFH domain and an interacting peptide from HEB. On the basis of the structure, key residues in AML1-ETO for HEB association were mutated. These mutations do not impair the ability of AML1-ETO to enhance the clonogenic capacity of primary mouse bone marrow cells and do not eliminate its ability to repress proliferation or granulocyte differentiation. Therefore, the eTAFH-E protein interaction appears to contribute relatively little to the activity of AML1-ETO.
Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.,Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck NA, Bushweller JH Blood. 2009 Apr 9;113(15):3558-67. Epub 2009 Feb 9. PMID:19204326[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
- ↑ Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck NA, Bushweller JH. Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity. Blood. 2009 Apr 9;113(15):3558-67. Epub 2009 Feb 9. PMID:19204326 doi:10.1182/blood-2008-06-161307
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