The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties

被引:69
作者
Bertolotti, A [1 ]
Bell, B [1 ]
Tora, L [1 ]
机构
[1] CNRS INSERM ULP, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch, France
关键词
oncogene; sarcoma; transcription factors II; histone acetylation; RNA polymerase II; recruitment;
D O I
10.1038/sj.onc.1203207
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In Ewing tumor, the (11;22) chromosomal translocation produces a chimeric molecule composed of the aminoterminal domain of EWS fused to the carboxyl-terminal DNA-binding domain of FLI-1. Previously, we have identified a novel protein TAF(II)68, which is highly similar to EWS and another closely related protein TLS (also called FUS), We demonstrate that the N-terminus of TAF(II)68 efficiently stimulates transcription when fused to two different DNA binding domains and that overexpression of TAF(II)68-FLI-1 chimeras in NIH3T3 cells leads to oncogenic transformation. We have also investigated the molecular mechanisms which account for the transcriptional activation ana the oncogenic transformation potential of the N-termini of TAF(II)68 and EWS, Thus, we have tested whether the artificial recruitment of components of the preinitiation complex (PIC) or a histone acetyltransferase (HAT) could bypass the requirement for the activation domains of either EWS or TAF(II)68. Recruitment of individual components of the transcription machinery or the GCN5 HAT is not sufficient to promote activation from FLI-1 responsive genes either in transfection experiments or in oncogenic transformation assays. These results suggest that the TAF(II)68 or EWS activation domains enhance a step after PIC formation in the transcriptional activation process.
引用
收藏
页码:8000 / 8010
页数:11
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