Mediator and human disease.
Mediator and human disease.
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DOI：
10.1016/j.semcdb.2011.07.024
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发表时间：
2011-09
影响因子：
7.3
通讯作者：
Boyer, Thomas G.
中科院分区：
文献类型：
--
作者：
Spaeth, Jason M.;Kim, Nam Hee;Boyer, Thomas G.
自近15年前发现酵母介质的后生动物以来，一系列生物化学和分子遗传学研究证实了它们的结构和功能关系，它们是信号激活转录因子传递的调控信息转导到RNA聚合酶II的综合枢纽。尽管如此，中介体复合体在进化过程中通过其组成亚基的数量和序列的实质性多样化和扩展而形成，这对多细胞生物的发展具有重要意义。在不同物种特异性起源的转录因子的后生动物中介复合物中，独特的相互作用表面的出现扩展了中介的作用，包括将发育编码信号与精确的基因表达输出耦合的基本功能，足以指定细胞的命运和功能。低等后生动物的遗传研究表明，Mediator在人类发育中的生物学意义，通过与遗传变异或其单个亚基的异常表达相关的人类病理的扩展列表得到了强调说明。在这里，我们回顾了目前关于个体中介亚基和特定病理疾病之间关联的知识体系。一旦建立，潜在的基因型-表型相关性的分子病因学就会得到解决，我们预计在这一关键领域的未来进展将有助于确定一系列人类病理的治疗靶点。
Since the identification of a metazoan counterpart to yeast Mediator nearly 15 years ago, a convergent body of biochemical and molecular genetic studies have confirmed their structural and functional relationship as an integrative hub through which regulatory information conveyed by signal activated transcription factors is transduced to RNA polymerase II. Nonetheless, metazoan Mediator complexes have been shaped during evolution by substantive diversification and expansion in both the number and sequence of their constituent subunits, with important implications for the development of multicellular organisms. The appearance of unique interaction surfaces within metazoan Mediator complexes for transcription factors of diverse species-specific origins extended the role of Mediator to include an essential function in coupling developmentally coded signals with precise gene expression output sufficient to specify cell fate and function. The biological significance of Mediator in human development, suggested by genetic studies in lower metazoans, is emphatically illustrated by an expanding list of human pathologies linked to genetic variation or aberrant expression of its individual subunits. Here, we review our current body of knowledge concerning associations between individual Mediator subunits and specific pathological disorders. When established, molecular etiologies underlying genotype-phenotype correlations are addressed, and we anticipate that future progress in this critical area will help identify therapeutic targets across a range of human pathologies.
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DOI：
10.1073/pnas.0401827101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Bruce, AW;Donaldson, IJ;Buckley, NJ
通讯作者：
Buckley, NJ
影响因子：
64.5
作者：
CHONG, JHA;TAPIARAMIREZ, J;MANDEL, G
通讯作者：
MANDEL, G
DOI：
10.1073/pnas.0709749105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Carrera, Ines;Janody, Florence;Treisman, Jessica E.
通讯作者：
Treisman, Jessica E.
影响因子：
5.3
作者：
Belakavadi, Madesh;Pandey, Pradeep K.;Fondell, Joseph D.
通讯作者：
Fondell, Joseph D.
影响因子：
158.5
作者：
Calle, EE;Rodriguez, C;Thun, MJ
通讯作者：
Thun, MJ