Functional analysis of TAND (TAF N-terminal domain) that inhibits TBP : DNA interactions

抑制 TBP 的 TAND（TAF N 末端结构域）的功能分析：DNA 相互作用

• 批准号: 09680677
• 负责人: KOKUBO Tetsuro
• 金额: $ 2.3万
• 依托单位: Nara Institute of Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680677/
• 关键词: transcription; TFIID; general transcription factor; TAF; TAND; activation; transcriptional regulation

TFIID is a multiprotein complex comprised of TBP and several TAFlls. Small N-terminal segments (TAND ; TAF N-terminal Domain) of Drosophila TAFll23O (dTAFll230) and yeast TAFll145 (yTAFll145) bind strongly to TBP and thereby inhibit TBP : DNA interactions. dTAFll230 TAND (dTAND) and yTAFll145 TAND (yTAND) were further divided into two subdomains, dTANDI (18-77 aa) & II(118-143 aa), and yTANDI (10-37 aa) & II(46-71 aa), respectively, that function cooperatively. More importantly, TANDI and TANDII compete with activators and TFIIA, respectively, for TBP binding. We also demonstrated the functional conservation between activation domains and TANDI.When fused to the DNA-binding domain, TANDI functions as an activation domain in yeast. Conversely, activation domains function as TANDI when TANDI is replaced with activation domains within TEIID.Furthermore, we show that the interaction with the concave surface of TBP is crucial for the functions of both activators and TAN DI.These results indicate that transcriptional activation steps include suppression of the inhibitory activity of TANDI by transcriptional activators.

TFIID是由TBP和几个TAFl组成的多蛋白复合体。果蝇TAFl1230(DTAFl1230)和酵母TAFl1245(YTAFll145)的小N-末端片段(tand；TAF N-末端结构域)与TBP强烈结合，从而抑制TBP与DNA的相互作用。DTAFl1230tand(DTAND)和yTAFl125tand(YTAND)进一步分为两个亚区，分别为dTANDI(18-77aa)和yTANDI(118-143aa)和yTANDI(10-37aa)和yTANDI(46-71aa)，它们具有协同作用。更重要的是，TANDI和TANDII分别与激活剂和TFIIA竞争TBP结合。我们还证明了激活结构域和TANDI之间的功能保守。当TANDI与DNA结合区域融合时，TANDI在酵母中起到激活结构域的作用。反之，当TANDI被TEIID中的激活结构域取代时，激活结构域起到TANDI的作用。此外，我们还表明，与TBP凹面的相互作用对于激活剂和TanDI的功能都是至关重要的。这些结果表明，转录激活步骤包括转录激活剂对Tandi抑制活性的抑制。

项目成果

Kokubo T et al: "The yeast TAF145 inhibitory domain and TFIIA competitively bind to TATA-binding protein" Mol.Cell.Biol.18(2). 1003-1012 (1998)

Kokubo T 等人：“酵母 TAF145 抑制结构域和 TFIIA 竞争性地结合 TATA 结合蛋白”Mol.Cell.Biol.18(2)。

Liu D et al: "Solution structure of a TBP-TAFII230 complex: Protein mimicry of the minor groove surface of the TATA box unwound by TBP" Cell. 94(5). 573-583 (1998)

Liu D 等人：“TBP-TAFII230 复合物的溶液结构：TBP 解绕的 TATA 盒小沟表面的蛋白质模拟”细胞。

Sakurai Y et al: "The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein 1b-binding protein.Mamushigin.from Agkistrodon halys blomhoffii venom" Thromb.Haemost.79. 1199-1207 (1998)

Sakurai Y 等人：“蛇毒血小板糖蛋白 1b 结合蛋白的 cDNA 克隆和分子特征。Mamushigin.from Agkistrodon halys blomhoffii 毒液”Thromb.Haemost.79。

Drysdale CM et al: "The Gcn4p activation domain interacts specifically in vitro with RNA polymerase II holoenzyme, TFIID, and the Adap-Gen5p coactivator complex" Molecular and Cellular Biology. 18(3). 1711-1724 (1998)

Drysdale CM 等人：“Gcn4p 激活结构域在体外与 RNA 聚合酶 II 全酶、TFIID 和 Adap-Gen5p 共激活复合物发生特异性相互作用”《分子和细胞生物学》。

Kokubo T et al: "The yeast TAF145 inhibitory domain and TFIIA competitively bind to TATA-binding protein" Moleculas and Cellular Biology. 18(2). 1003-1012 (1998)

Kokubo T 等人：“酵母 TAF145 抑制结构域和 TFIIA 竞争性地结合 TATA 结合蛋白”《分子与细胞生物学》。