REDUCED LEVELS OF HSP90 COMPROMISE STEROID-RECEPTOR ACTION INVIVO
REDUCED LEVELS OF HSP90 COMPROMISE STEROID-RECEPTOR ACTION INVIVO
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DOI：
10.1038/348166a0
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发表时间：
1990-11-08
期刊：
影响因子：
64.8
通讯作者：
YAMAMOTO, KR
中科院分区：
文献类型：
--
作者：
PICARD, D;KHURSHEED, B;YAMAMOTO, KR
类固醇激素的信号是由受体蛋白介导的，受体蛋白结合激素配体并调节特定基因的转录。热休克蛋白HSP90似乎选择性地与未连接的受体(apo受体)结合，但这种相互作用是否影响体内受体的功能尚未确定。为了解决HSP90的作用，我们利用了哺乳动物类固醇受体在酵母1-4中发挥作用的能力。我们构建了一株HSP90表达可调控的酿酒酵母，与野生型相比，HSP90的表达可以减少20倍以上。在低水平的HSP90水平下，载脂蛋白受体似乎大部分不含HSP90，但未能促进转录；在激素添加时，受体被激活，但效率显著降低。因此，HSP90并不仅仅通过空间干扰来抑制受体的功能；相反，HSP90似乎促进了脱辅基受体对激素信号的后续反应。这是HSP90在类固醇受体信号转导途径中发挥作用的第一个生物学证据。
SIGNALLING by steroid hormones is mediated by receptor proteins that bind hormonal ligands and regulate the transcription of specific genes. The heat-shock protein hsp90 seems to associate selectively with unliganded receptors (aporeceptors), but it has not been determined whether this interaction affects receptor functionin vivo. To address the role of hsp90, we have taken advantage of the capacity of mammalian steroid receptors to function in yeast1–4. We constructed a strain ofSaccharomyces cerevisiaein which hsp90 expression was regulatable and could be reduced more than 20-fold relative to wild type. At low levels of hsp90, aporeceptors seem to be mostly hsp90-free, yet fail to enhance transcription; on hormone addition, the receptors are activated but with markedly reduced efficiency. Thus hsp90 does not inhibit receptor function solely by steric interference; rather, hsp90 seems to facilitate the subsequent response of the aporeceptor to the hormonal signal. This is the first biological evidence that hsp90 acts in the signal transduction pathway for steroid receptors.