2knh
From Proteopedia
The Solution structure of the eTAFH domain of AML1-ETO complexed with HEB peptide
Structural highlights
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 ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAML1-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
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