Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1107, USA.
Future Med Chem. 2013 Jun;5(9):1059-71. doi: 10.4155/fmc.13.88.
Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.
Hsp90 是一种分子伴侣，也是稳定和激活几种致癌蛋白的重要驱动因素，这些蛋白参与肿瘤细胞的恶性转化。因此，Hsp90 被报道为几种肿瘤的治疗有希望的靶点，如非小细胞肺癌和 HER2 阳性乳腺癌，这并不奇怪。Hsp90 伴侣功能取决于其结合和水解 ATP 的能力，并且已经表明 Hsp90 抑制剂能够与核苷酸竞争结合 Hsp90。多种因素，如共伴侣和翻译后修饰，参与调节 Hsp90 ATP 酶活性。在这里，我们综述了翻译后修饰和共伴侣对 Hsp90 抑制剂疗效的影响。
