Khurana Nidhi, Bhattacharyya Sunanda
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad , Hyderabad , India.
Front Oncol. 2015 Apr 28;5:100. doi: 10.3389/fonc.2015.00100. eCollection 2015.
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.
在过去十年中，热休克蛋白90（Hsp90）已成为癌细胞生长和增殖的主要调节因子。在癌细胞中，它有助于致癌蛋白（包括几种激酶和转录因子（TF））的成熟。最近的研究表明，除了其伴侣活性外，它还对转录机制进行调节，从而改变细胞生理学。Hsp90及其共伴侣至少在三个不同水平上调节转录。首先，它们响应各种生理信号改变某些转录因子的稳态水平。其次，它们调节某些表观遗传修饰因子（如组蛋白脱乙酰酶或DNA甲基转移酶）的活性，从而对环境变化做出反应。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。在本综述中，我们将以各种模式生物为例，特别强调癌症进展，讨论Hsp90在上述三种转录控制机制中的作用。
