Thut C J, Chen J L, Klemm R, Tjian R
Howard Hughes Medical Institute, University of California, Berkeley 94720.
Science. 1995 Jan 6;267(5194):100-4. doi: 10.1126/science.7809597.
The tumor suppressor protein p53 is a transcriptional regulator that enhances the expression of proteins that control cellular proliferation. The multisubunit transcription factor IID (TFIID) is thought to be a primary target for site-specific activators of transcription. Here, a direct interaction between the activation domain of p53 and two subunits of the TFIID complex, TAFII40 and TAFII60, is reported. A double point mutation in the activation domain of p53 impaired the ability of this domain to activate transcription and, simultaneously, its ability to interact with both TAFII40 and TAFII60. Furthermore, a partial TFIID complex containing Drosophila TATA binding protein (dTBP), human TAFII250, dTAFII60, and dTAFII40 supported activation by a Gal4-p53 fusion protein in vitro, whereas TBP or a subcomplex lacking TAFII40 and TAFII60 did not. Together, these results suggest that TAFII40 and TAFII60 are important targets for transmitting activation signals between p53 and the initiation complex.
肿瘤抑制蛋白p53是一种转录调节因子，可增强控制细胞增殖的蛋白质的表达。多亚基转录因子IID（TFIID）被认为是转录位点特异性激活因子的主要靶点。在此，报道了p53的激活结构域与TFIID复合物的两个亚基TAFII40和TAFII60之间的直接相互作用。p53激活结构域中的双点突变损害了该结构域激活转录的能力，同时也损害了其与TAFII40和TAFII60相互作用的能力。此外，含有果蝇TATA结合蛋白（dTBP）、人TAFII250、dTAFII60和dTAFII40的部分TFIID复合物在体外支持Gal4-p53融合蛋白的激活，而TBP或缺乏TAFII40和TAFII60的亚复合物则不能。这些结果共同表明，TAFII40和TAFII60是在p53和起始复合物之间传递激活信号的重要靶点。
