Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code.
Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code.
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DOI：
10.1093/nar/gkt657
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发表时间：
2013-10
影响因子：
14.9
通讯作者：
Inga A
中科院分区：
文献类型：
--
作者：
Ciribilli Y;Monti P;Bisio A;Nguyen HT;Ethayathulla AS;Ramos A;Foggetti G;Menichini P;Menendez D;Resnick MA;Viadiu H;Fronza G;Inga A
结构和生物化学研究表明，p73、p63和p53识别具有相同氨基酸和相似结合亲和力的DNA。在这里，测量大量的反应元件（RE）在酵母和人类细胞系的反式激活活性，我们表明，p53家族蛋白也有重叠的反式激活配置文件。我们确定了DNA结合结构域中L1和L3环保守氨基酸的突变，这些突变在p73、p63和p53中几乎同等地调节反式激活潜力。例如，p73中的突变体S139 F对所选RE具有更高的反式激活潜力，体外增强的DNA结合协同性和如在蛋白质-DNA复合物的晶体结构中所见的柔性环L1。通过研究，RE序列的变化如何影响反式激活特异性，我们发现了一个RE反式激活代码，预测增强的反式激活;这种相关性更强的启动子与细胞凋亡相关的基因。
Structural and biochemical studies have demonstrated that p73, p63 and p53 recognize DNA with identical amino acids and similar binding affinity. Here, measuring transactivation activity for a large number of response elements (REs) in yeast and human cell lines, we show that p53 family proteins also have overlapping transactivation profiles. We identified mutations at conserved amino acids of loops L1 and L3 in the DNA-binding domain that tune the transactivation potential nearly equally in p73, p63 and p53. For example, the mutant S139F in p73 has higher transactivation potential towards selected REs, enhanced DNA-binding cooperativity in vitro and a flexible loop L1 as seen in the crystal structure of the protein–DNA complex. By studying, how variations in the RE sequence affect transactivation specificity, we discovered a RE-transactivation code that predicts enhanced transactivation; this correlation is stronger for promoters of genes associated with apoptosis.
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影响因子：
56.9
作者：
CHO, YJ;GORINA, S;PAVLETICH, NP
通讯作者：
PAVLETICH, NP
影响因子：
8
作者：
Aylon, Y.;Yabuta, N.;Besserglick, H.;Buganim, Y.;Rotter, V.;Nojima, H.;Oren, M.
通讯作者：
Oren, M.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.2
作者：
Emamzadah, Soheila;Tropia, Laurence;Halazonetis, Thanos D.
通讯作者：
Halazonetis, Thanos D.
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A