Bereczki Orsolya, Ujfaludi Zsuzsanna, Pardi Norbert, Nagy Zita, Tora Laszlo, Boros Imre M, Balint Eva
Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
BMC Mol Biol. 2008 Jun 12;9:57. doi: 10.1186/1471-2199-9-57.
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.
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.
We identified TAF3 as an evolutionarily conserved negative regulator of p53 transcription activation function.
肿瘤抑制蛋白p53是一种序列特异性DNA结合转录调节因子，它通过影响大量基因的表达在基因组保护和细胞凋亡中发挥多种作用。为了更好地理解p53转录功能的调控机制，我们研究了p53的相互作用。
我们鉴定出BIP2（Bric-à-brac相互作用蛋白2），它是TAF3的果蝇同源物，TAF3是TFIID的一个含有组蛋白折叠和植物同源结构域的亚基，是黑腹果蝇p53（Dmp53）的一个相互作用伙伴。我们在酵母双杂交试验和体外实验中均检测到Dmp53的C末端与TAF3的中央区域之间存在物理相互作用。有趣的是，DmTAF3也能与人p53相互作用，而哺乳动物的TAF3能与Dmp53和人p53都结合。这种进化上保守的相互作用在功能上具有重要意义，因为在人类细胞系中，TAF3表达的升高会严重且选择性地抑制p53的转录激活，并且还会降低p53蛋白的水平。
我们鉴定出TAF3是p53转录激活功能的一种进化上保守的负调节因子。
