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The hTAF II 68‐TEC fusion protein functions as a strong transcriptional activator
Author(s) -
Kim Sol,
Lee Hye Jin,
Jun Hee Jung,
Kim Jungho
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23379
Subject(s) - tec , transactivation , fusion protein , biology , fusion gene , transcription factor , microbiology and biotechnology , chemistry , cancer research , gene , genetics , recombinant dna , physics , ionosphere , astronomy
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. © 2008 Wiley‐Liss, Inc.