p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60.
The tumor suppressor protein p53 is a transcriptional regulator that enhances the expression of proteins that control cellular proliferation. The multisubunit transcription factor IID (TFIID) is thought to be a primary target for site-specific activators of transcription. Here, a direct interaction between the activation domain of p53 and two subunits of the TFIID complex, TAFII40 and TAFII60, is reported. A double point mutation in the activation domain of p53 impaired the ability of this domain to activate transcription and, simultaneously, its ability to interact with both TAFII40 and TAFII60. Furthermore, a partial TFIID complex containing Drosophila TATA binding protein (dTBP), human TAFII250, dTAFII60, and dTAFII40 supported activation by a Gal4-p53 fusion protein in vitro, whereas TBP or a subcomplex lacking TAFII40 and TAFII60 did not. Together, these results suggest that TAFII40 and TAFII60 are important targets for transmitting activation signals between p53 and the initiation complex.
Thut
C J
CJ
Howard Hughes Medical Institute, University of California, Berkeley 94720.
Chen
J L
JL
Klemm
R
R
Tjian
R
R
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators / Q000378:metabolism*; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C084120:e(y)1 protein, Drosophila; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa