Hsp90, the concertmaster: tuning transcription.
Hsp90, the concertmaster: tuning transcription.
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DOI：
10.3389/fonc.2015.00100
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发表时间：
2015
影响因子：
4.7
通讯作者：
Bhattacharyya S
中科院分区：
文献类型：
--
作者：
Khurana N;Bhattacharyya S
在过去的十年中，Hsp90已成为癌细胞生长和增殖的主要调节因子。在癌细胞中，它有助于使致癌蛋白质成熟，包括几种激酶和转录因子（TF）。最近的研究表明，除了它的伴侣活性，它还赋予转录机制的调节，从而改变细胞生理学。热休克蛋白90及其辅分子伴侣至少在三个不同的水平上调节转录。首先，它们改变某些TF的稳态水平以响应各种生理线索。其次，它们调节某些表观遗传修饰剂的活性，如组蛋白脱乙酰基酶或DNA甲基转移酶，从而对环境的变化做出反应。第三，它们参与从某些基因的启动子区域驱逐组蛋白，从而开启基因表达。在这篇综述中，我们讨论了热休克蛋白90在所有上述三种转录控制机制中的作用，以各种模式生物为例，特别强调癌症的进展。
In the last decade, Hsp90 has emerged as a major regulator of cancer cell growth and proliferation. In cancer cells, it assists in giving maturation to oncogenic proteins including several kinases and transcription factors (TF). Recent studies have shown that apart from its chaperone activity, it also imparts regulation of transcription machinery and thereby alters the cellular physiology. Hsp90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain TFs in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. In this review, we discuss the role of Hsp90 in all the three aforementioned mechanisms of transcriptional control, taking examples from various model organisms with a special emphasis on cancer progression.
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