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首页> 外文期刊>Cell Research >Geldanamycin induces CHOP expression through a 4-(2-aminoethyl)-benzenesulfonyl fluoride-responsive serine protease
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Geldanamycin induces CHOP expression through a 4-(2-aminoethyl)-benzenesulfonyl fluoride-responsive serine protease

机译：格尔德霉素通过4-（2-氨基乙基）-苯磺酰氟响应丝氨酸蛋白酶诱导CHOP表达

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Geldanamycin is a benzoquinone ansamycin, which was originally described as a tyrosine kinase inhibitor. However, subsequent studies have revealed that geldanamycin binds to and inhibits heat-shock protein 90 (Hsp90) activity [1]. Hsp90 is a molecular chaperone involved in the con-formational maturation of proteins such as mutated p53, Raf-1, Akt, Bcr-Abl, and ErbB2. It is suggested that agents inhibiting Hsp90 have anti-cancer properties, although the precise molecular mechanisms underlying the anti-cancer effects of geldanamycin are not well understood.rnIncreasing evidence has suggested that diabetes and neurodegenerative disorders such as Parkinson's and Alzheimer's diseases are related to the disruption of endoplasmic reticulum (ER) function. In response to ER stress, unfolded proteins accumulate and aggregate in the ER, which will trigger many rescuer responses, including the unfolded protein response (UPR) and ER-associated degradation. Interestingly, geldanamycin has been shown to upregulate ER chaperones and the expression of CHOP [2]. Moreover, Hsp90 associates with PERK and IRE la, ER-resident trans-membrane protein kinases involved in ER stress response [3], These observations suggest that Hsp90 is involved in ER stress response and may play an important role in ER stress-related diseases. Therefore,rnwe investigated the potential mechanism by which geldanamycin affects ER stress using the L929 fibroblastoma cell line.
机译：格尔德霉素是苯醌安沙霉素，最初被描述为酪氨酸激酶抑制剂。然而，随后的研究表明，格尔德霉素与热激蛋白90（Hsp90）结合并抑制其活性[1]。 Hsp90是分子伴侣，参与蛋白质的构象成熟，例如突变的p53，Raf-1，Akt，Bcr-Abl和ErbB2。尽管尚不完全了解格尔德霉素抗癌作用的确切分子机制，但有人认为抑制Hsp90的药物具有抗癌作用。越来越多的证据表明，糖尿病和帕金森氏病和阿尔茨海默氏病等神经退行性疾病与内质网（ER）功能的破坏。响应于内质网应激，未折叠的蛋白质在内质网中积累和聚集，这将触发许多拯救者反应，包括未折叠的蛋白质响应（UPR）和与内质网相关的降解。有趣的是，格尔德霉素已显示出上调ER伴侣和CHOP的表达[2]。此外，Hsp90与参与ER应激反应的ER驻留跨膜蛋白激酶PERK和IREla有关[3]。这些观察结果表明，Hsp90参与ER应激反应，并且可能在ER应激相关疾病中发挥重要作用。因此，我们使用L929成纤维细胞瘤细胞系研究了格尔德霉素影响内质网应激的潜在机制。

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