p53 Transcriptional Activation Mediated by Coactivators TAF II 40 and TAF II 60

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, TAF II 40 and TAF II 60, 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 TAF II 40 and TAF II 60. Furthermore, a partial TFIID complex containing Drosophila TATA binding protein (dTBP), human TAF II 250, dTAF II 60, and dTAF II 40 supported activation by a Gal4-p53 fusion protein in vitro, whereas TBP or a subcomplex lacking TAF II 40 and TAF II 60 did not. Together, these results suggest that TAF II 40 and TAF II 60 are important targets for transmitting activation signals between p53 and the initiation complex.