Prolyl isomerases in gene transcription.

Prolyl isomerases in gene transcription.
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DOI:
10.1016/j.bbagen.2014.10.028
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发表时间:
2015-10
影响因子:
3
通讯作者:
Hanes, Steven D.
Hanes, Steven D.
中科院分区:
生物学3区
文献类型:
--
作者:
Hanes, Steven D.

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肽基脯氨酰异构酶 (PPIase) 是帮助新合成蛋白质折叠并调节成熟蛋白质的稳定性、定位和活性的酶。它们通过催化脯氨酸之前的肽键的可逆(顺反)旋转来实现这一点,从而诱导目标蛋白质的构象变化。本综述将讨论 PPIase 如何通过控制 (1) DNA 结合转录调节蛋白、(2) RNA 聚合酶 II 和 (3) 染色质和组蛋白修饰酶的活性来调节基因转录。每个 PPIase 家族的成员(亲环蛋白、FKBP 和小病毒蛋白)在多个水平上调节基因转录。除了少数情况外,在所有情况下,确切的机制仍然难以捉摸。结构研究、特定抑制剂的开发以及研究体内顺式/反式异构化的新方法代表了这个融合了两个重要领域的新领域的一些挑战。脯氨酰异构酶已被发现在转录过程的所有阶段发挥关键的调节作用。此外,PPIs 控制上游信号通路,调节发育、激素反应和环境应激过程中的基因特异性转录。更广泛地说,尽管转录在酶和结构蛋白的生产中通常是限速的,但转录后修饰也很关键,并且 PPIase 在这里也发挥着关键作用(请参阅本期的其他评论)。
Peptidyl-prolyl isomerases (PPIases) are enzymes that assist in the folding of newly-synthesized proteins and regulate the stability, localization, and activity of mature proteins. They do so by catalyzing reversible (cis-trans) rotation about the peptide bond that precedes proline, inducing conformational changes in target proteins. This review will discuss how PPIases regulate gene transcription by controlling the activity of (1) DNA-binding transcription regulatory proteins, (2) RNA polymerase II, and (3) chromatin and histone modifying enzymes. Members of each family of PPIase (cyclophilins, FKBPs, and parvulins) regulate gene transcription at multiple levels. In all but a few cases, the exact mechanisms remain elusive. Structure studies, development of specific inhibitors, and new methodologies for studying cis/trans isomerization in vivo represent some of the challenges in this new frontier that merges two important fields. Prolyl isomerases have been found to play key regulatory roles in all phases of the transcription process. Moreover, PPIases control upstream signaling pathways that regulate gene-specific transcription during development, hormone response and environmental stress. More broadly, although transcription is often rate-limiting in the production of enzymes and structural proteins, post-transcriptional modifications are also critical, and PPIases play key roles here as well (see other reviews in this issue).
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