Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human extraskeletal myxoid chondrosarcoma (EMC) is caused by a chromosomal translocation that involves TEC (translocated in extraskeletal myxoid chondrosarcoma), and either EWS (Ewing's sarcoma) or hTAF(II)68 (human TATA-binding protein-associated factor II 68), which generates EWS-TEC or hTAF(II)68-TEC fusion proteins, respectively. Although there has been a great deal of progress in characterizing EWS-TEC, there is relatively little known about the biological function of hTAF(II)68-TEC. We have examined the functional consequences of the fusion of the amino terminal domain (NTD) of hTAF(II)68 to TEC in EMC. The chimeric gene encodes a nuclear protein that binds DNA with the same sequence specificity as parental TEC. Nuclear localization of hTAF(II)68-TEC was dependent on the DNA binding domain, and we identified a cluster of basic amino acids in the DNA binding domain, KRRR, that specifically mediate the nuclear localization of hTAF(II)68-TEC. The transactivation activity of hTAF(II)68-TEC was higher than TEC towards a known target promoter that contained several TEC binding sites. Finally, deletion analysis of hTAF(II)68-TEC indicated that the hTAF(II)68 NTD, and the AF1 and AF2 domains of hTAF(II)68-TEC are necessary for full transactivation potential. These results suggest that the oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein produces a gain of function chimeric product.
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PMID:The hTAF II 68-TEC fusion protein functions as a strong transcriptional activator. 1833 Sep 2

MTG8 (RUNX1T1) is a fusion partner of AML1 (RUNX1) in the leukemic chromosome translocation t(8;21). The AML1-MTG8 fusion gene encodes a chimeric transcription factor. One of the highly conserved domains of MTG8 is TAFH which possesses homology with human TAF4 [TATA-box binding protein-associated factor]. To obtain specific inhibitors of the AML1-MTG8 fusion protein, we isolated RNA aptamers against the MTG8 TAFH domain using systematic evolution of ligands by exponential enrichment. All TAF aptamers contained guanine-rich sequences. Analyses of a TAF aptamer by NMR, CD, and mutagenesis revealed that it forms a parallel G-quadruplex structure in the presence of K+ . Furthermore, the aptamer could bind to the AML1-MTG8 fusion protein and dissociate the AML1-MTG8/DNA complex, suggesting that it can inhibit the dominant negative effects of AML1-MTG8 against normal AML1 function and serve as a potential therapeutic agent for leukemia.
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PMID:A G-quadruplex-forming RNA aptamer binds to the MTG8 TAFH domain and dissociates the leukemic AML1-MTG8 fusion protein from DNA. 3287 May 1