TATA binding protein associated factor 3 (TAF3) interacts with p53 and inhibits its function

Orsolya Bereczki¹ , Zsuzsanna Ujfaludi¹ , Norbert Pardi² , Zita Nagy³ , Laszlo Tora³ , Imre M Boros¹^,2 and Eva Balint¹^,4

¹Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary

²Institute of Biochemistry, Biological Research Center, Szeged, Hungary

³Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), UMR 7104 CNRS, ULP, INSERM U.596, Illkirch, Strasbourg, France

⁴BayGen Institute, Bay Zoltan Foundation for Applied Research, Szeged, Hungary

author email corresponding author email

BMC Molecular Biology 2008, 9:57doi:10.1186/1471-2199-9-57


Published:	12 June 2008

Abstract

Background

The tumour suppressor protein p53 is a sequence specific DNA-binding transcription regulator, which exerts its versatile roles in genome protection and apoptosis by affecting the expression of a large number of genes. In an attempt to obtain a better understanding of the mechanisms by which p53 transcription function is regulated, we studied p53 interactions.

Results

We identified BIP2 (Bric-à-brac interacting protein 2), the fly homolog of TAF3, a histone fold and a plant homeodomain containing subunit of TFIID, as an interacting partner of Drosophila melanogaster p53 (Dmp53). We detected physical interaction between the C terminus of Dmp53 and the central region of TAF3 both in yeast two hybrid assays and in vitro. Interestingly, DmTAF3 can also interact with human p53, and mammalian TAF3 can bind to both Dmp53 and human p53. This evolutionarily conserved interaction is functionally significant, since elevated TAF3 expression severely and selectively inhibits transcription activation by p53 in human cell lines, and it decreases the level of the p53 protein as well.

Conclusion

We identified TAF3 as an evolutionarily conserved negative regulator of p53 transcription activation function.