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.

中文翻译：

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TATA 结合蛋白相关因子 3 (TAF3) 与 p53 相互作用并抑制其功能。

背景肿瘤抑制蛋白p53是一种序列特异性的DNA结合转录调节因子，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其多功能作用。为了更好地了解 p53 转录功能的调节机制，我们研究了 p53 相互作用。结果我们确定了 BIP2（Bric-à-brac 相互作用蛋白 2），TAF3 的果蝇同源物，一个组蛋白折叠和一个含有 TFIID 亚基的植物同源域，作为果蝇 p53 (Dmp53) 的相互作用伙伴。我们在酵母两种杂交试验和体外检测到 Dmp53 的 C 末端和 TAF3 的中心区域之间的物理相互作用。有趣的是，DmTAF3 也可以与人 p53 相互作用，哺乳动物 TAF3 可以与 Dmp53 和人 p53 结合。这种进化上保守的相互作用在功能上很重要，因为升高的 TAF3 表达严重且选择性地抑制了 p53 在人类细胞系中的转录激活，并且它也降低了 p53 蛋白的水平。结论 我们将 TAF3 鉴定为 p53 转录激活功能的进化上保守的负调节因子。