Stat protein transactivation domains recruit p300/CBP through widely divergent sequences
Stat protein transactivation domains recruit p300/CBP through widely divergent sequences
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DOI：
10.1074/jbc.274.36.25343
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发表时间：
1999-09-03
影响因子：
4.8
通讯作者：
Levy, DE
中科院分区：
文献类型：
--
作者：
Paulson, M;Pisharody, S;Levy, DE
信号转导和转录激活因子（Stat）基因家族在整个进化过程中高度保守。基因复制和分化产生了7个哺乳动物Stat基因，每个基因都介导一个不同的过程。虽然一些Stat蛋白被多种细胞因子激活，但Stat 2对I型干扰素的反应具有高度特异性，我们克隆了小鼠Stat 2，发现尽管其序列与其人类同源物的差异大于任何其他小鼠-人类Stat对，但它甚至在人类细胞中也具有完全功能。与其他Stab基因85-99%的相似性相比，总体序列同一性仅为69%，并且在两个物种中仍然发挥相似或相同功能的几个单独结构域甚至更不保守。负责与IRF 9相互作用的卷曲螺旋结构域只有65%相同，但小鼠Stat 2与人或小鼠IRFS相互作用;羧基末端只有30%相同，但两个区域都具有相同的反式激活结构域。小鼠和人的反式激活结构域招募p300/CBP共激活因子，并同样敏感的腺病毒E1 A蛋白的抑制。有趣的是，Stat 3的羧基末端也作为一个反式激活剂能够招募p300/CBP，就像Stat 1蛋白一样，虽然有很大的不同效力。然而，这些蛋白质与Stat 2没有序列相似性，这些数据表明，高度分歧的一级序列可以提供相似或相同的功能，并且人和小鼠Stat 2之间的最小相似区域可以定义功能的关键决定因素。
The signal transduction and activator of transcription (Stat) gene family has been highly conserved throughout evolution. Gene duplication and divergence has produced 7 mammalian Stat genes, each of which mediates a distinct process. While some Stat proteins are activated by multiple cytokines, Stat2 is highly specific for responses to type I interferon, We have cloned mouse Stat2 and found that while its sequence was more divergent from its human homologue than any other mouse-human Stat pairs, it was fully functional even in human cells. Overall sequence identity was only 69%, compared with 85-99% similarity for other Stab genes, and several individual domains that still served similar or identical functions in both species were even less well conserved. The coiled-coil domain responsible for interaction with IRF9 was only 65% identical and yet mouse Stat2 interacted with either human or mouse IRFS; the carboxyl terminus was only 30% identical and yet both regions functioned as equal transactivation domains. Both mouse and human transactivation domains recruited the p300/CBP coactivator and were equally sensitive to inhibition by adenovirus E1A protein. Interestingly, the Stat3 carboxyl terminus also functioned as a transactivator capable of recruiting p300/CBP, as does the Stat1 protein, although with widely differing potencies. Yet these proteins share no sequence similarity with Stat2, These data demonstrate that highly diverged primary sequences can serve similar or identical functions, and that the minimal regions of similarity between human and mouse Stat2 may define the critical determinants for function.