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

Orsolya Bereczki,Norbert Pardi,Zsuzsanna Ujfaludi,Eva Balint,Laszlo Tora,Zita Nagy,Imre M Boros

doi:10.1186/1471-2199-9-57

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionWe identified TAF3 as an evolutionarily conserved negative regulator of p53 transcription activation function.

Highlights

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
Drosophila melanogaster p53 (Dmp53) interacts with BIP2/Drosophila melanogaster TATA binding protein associated factor 3 (TAF3) (DmTAF3) In order to identify Dmp53-interacting partners, we screened Drosophila embryonic cDNA library with the yeast two-hybrid (Y2H) method using Dmp53 fused to lexA DNA binding domain (DBD) as bait
We tried to delineate the C-terminal binding region of Dmp53, and we found that the oligomerization domain alone interacted strongly, and the basic regulatory domain alone interacted weakly with DmTAF3 (Fig. 1C)

Summary

Introduction

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. The p53 tumour suppressor protein orchestrates cellular response to genotoxic stress such as DNA damage, activated oncogenes and other metabolic changes [1]. P53 is kept at a low level through the action of various ubiquitin ligases [2], while cellular stress results in the stabilization of p53 and its activation as a transcription factor. Activated p53 is able to induce cell death via transcription-independent ways [3], importantly, it influences the transcription of a large number of genes, that in turn promote cell cycle arrest, DNA repair or apoptosis [4]. The multiple mechanisms that stabilize and activate p53 include post-translational modifications and interactions with different co-factors. Activation of p53 upon UV radiation is less well understood, among other mechanisms, it may (page number not for citation purposes)

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