Expressed as the sole Hsp90 of yeast, the α and β isoforms of human Hsp90 differ with regard to their capacities for activation of certain client proteins, whereas only Hsp90β generates sensitivity to the Hsp90 inhibitor radicicol
Expressed as the sole Hsp90 of yeast, the α and β isoforms of human Hsp90 differ with regard to their capacities for activation of certain client proteins, whereas only Hsp90β generates sensitivity to the Hsp90 inhibitor radicicol
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DOI：
10.1111/j.1742-4658.2007.05974.x
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发表时间：
2007-09-01
期刊：
影响因子：
5.4
通讯作者：
Piper, Peter W.
中科院分区：
文献类型：
--
作者：
Millson, Stefan H.;Truman, Andrew W.;Piper, Peter W.
热休克蛋白90（Hsp 90）是真核细胞中许多最重要的调节蛋白（Hsp 90“客户”）的活性所需的分子伴侣。脊椎动物具有两种胞质Hsp 90同种型，Hsp 90 α和Hsp 90 β。Hsp 90 β在大多数组织中组成性表达至高水平，并且通常比Hsp 90 α更丰富，而Hsp 90 α是应激诱导的，并且在许多癌细胞中过表达。作为酵母的唯一Hsp 90表达，人Hsp 90 α和Hsp 90 β都能够提供必需的Hsp 90功能。某些热休克蛋白90客户端（热休克转录因子，v-src）的激活更有效的热休克蛋白90 α，而不是热休克蛋白90 β，存在于酵母中。相反，某些其他客户端（糖皮质激素受体，细胞外信号调节激酶-5丝裂原活化蛋白激酶）的激活受这些细胞中存在的人Hsp 90亚型的影响较小。值得注意的是，尽管Hsp 90 β作为酵母的唯一Hsp 90的表达使细胞对Hsp 90抑制剂根赤霉素高度敏感，但Hsp 90 α的相当表达却没有。这提出了一种明显的可能性，即对于哺乳动物系统，Hsp 90 α/Hsp 90 β比值的改变（与热休克一样）可能是影响细胞对Hsp 90抑制剂敏感性的重要因素。
Heat shock protein 90 (Hsp90) is a molecular chaperone required for the activity of many of the most important regulatory proteins of eukaryotic cells (the Hsp90 'clients'). Vertebrates have two isoforms of cytosolic Hsp90, Hsp90 alpha and Hsp90 beta. Hsp90 beta is expressed constitutively to a high level in most tissues and is generally more abundant than Hsp90 alpha, whereas Hsp90 alpha is stress-inducible and overexpressed in many cancerous cells. Expressed as the sole Hsp90 of yeast, human Hsp90 alpha and Hsp90 beta are both able to provide essential Hsp90 functions. Activations of certain Hsp90 clients (heat shock transcription factor, v-src) were more efficient with Hsp90 alpha, rather than Hsp90 beta, present in the yeast. In contrast, activation of certain other clients (glucocorticoid receptor; extracellular signal-regulated kinase-5 mitogen-activated protein kinase) was less affected by the human Hsp90 isoform present in these cells. Remarkably, whereas expression of Hsp90 beta as the sole Hsp90 of yeast rendered cells highly sensitive to the Hsp90 inhibitor radicicol, comparable expression of Hsp90 alpha did not. This raises the distinct possibility that, also for mammalian systems, alterations to the Hsp90 alpha/Hsp90 beta ratio (as with heat shock) might be a significant factor affecting cellular susceptibility to Hsp90 inhibitors.