Transcription factor TFIID is a direct functional target of the adenovirus E1A transcription-repression domain.
Transcription factor TFIID is a direct functional target of the adenovirus E1A transcription-repression domain.
复制标题
转录因子 TFIID 是腺病毒 E1A 转录抑制结构域的直接功能靶标。
DOI：
10.1073/pnas.92.22.10330
复制
发表时间：
1995
影响因子：
11.1
通讯作者：
Green,M
中科院分区：
文献类型：
--
作者：
Song,CZ;Loewenstein,PM;Toth,K;Green,M
243个氨基酸的腺病毒E1 A癌蛋白对参与细胞生长调节的细胞基因的表达进行正性和负性调节。E1 A转录抑制功能似乎与其诱导细胞DNA合成、细胞增殖和细胞转化以及抑制细胞分化的能力有关。E1 A抑制各种启动子转录的机制已被证明是谜。在这里，我们提供了几条线的证据表明，“TATA盒”结合蛋白（TBP）的转录因子TFIID的组成部分是E1 A的N-末端80个氨基酸内编码的E1 A阻遏功能的细胞目标。(i)E1 A N-末端80个氨基酸[E1 A-（1-80）蛋白]在体外有效地抑制来自含TATA的核心启动子的基础转录。(ii)TBP在体外完全逆转E1 A的阻遏。(iii)TBP恢复E1 A-（1-80）蛋白亲和力耗尽的核提取物的转录活性。(iv)E1 A的N端阻遏结构域在体外直接特异性地与TBP相互作用。这些结果可能有助于解释E1 A如何抑制一组缺乏共同上游启动子元件的基因。
The 243-amino acid adenovirus E1A oncoprotein both positively and negatively modulates the expression of cellular genes involved in the regulation of cell growth. The E1A transcription repression function appears to be linked with its ability to induce cellular DNA synthesis, cell proliferation, and cell transformation, as well as to inhibit cell differentiation. The mechanism by which E1A represses the transcription of various promoters has proven enigmatic. Here we provide several lines of evidence that the "TATA-box" binding protein (TBP) component of transcription factor TFIID is a cellular target of the E1A repression function encoded within the E1A N-terminal 80 amino acids. (i) The E1A N-terminal 80 amino acids [E1A-(1-80)protein] efficiently represses basal transcription from TATA-containing core promoters in vitro. (ii) TBP reverses completely E1A repression in vitro. (iii) TBP restores transcriptional activity to E1A-(1-80) protein affinity-depleted nuclear extracts. (iv) The N-terminal repression domain of E1A interacts directly and specifically with TBP in vitro. These results may help explain how E1A represses a set of genes that lack common upstream promoter elements.