The hTAF II 68-TEC fusion protein functions as a strong transcriptional activator

Int J Cancer. 2008 Jun 1;122(11):2446-53. doi: 10.1002/ijc.23379.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Bone Neoplasms / genetics
  • Chondrosarcoma / genetics*
  • Chondrosarcoma / pathology
  • Chromosomes, Human, Pair 17
  • Chromosomes, Human, Pair 9
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Sarcoma, Ewing / genetics*
  • Sarcoma, Ewing / pathology
  • TATA-Binding Protein Associated Factors / genetics*
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Translocation, Genetic*


  • DNA Primers
  • TAF15 protein, human
  • TATA-Binding Protein Associated Factors
  • Transcription Factors