Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
J Biochem. 2012 Sep;152(3):209-11. doi: 10.1093/jb/mvs072. Epub 2012 Jul 3.
Yes-associated protein (YAP) has been shown to play a critical role in the growth of various tumours. Phosphorylation of Ser127 of YAP leads to the inhibition of YAP translocation into nucleus and subsequent failure to regulate the expression of target genes that induce cell proliferation. Chemical manipulation of YAP localization or expression may provide an efficient method for cancer treatment. In a recent work published by Bao et al. (J. Biochem. 2011;150:199-208), various compounds were screened in human osteosarcoma cells that stably express Green Fluorescent Protein-labeled YAP by monitoring subcellular localization of GFP-YAP. Using this cell-based assay, they found that dobutamine, a β-adrenergic receptor agonist, attenuated YAP-dependent transcription by inhibiting its nuclear translocation. The authors suggest dobutamine as a possible drug for cancer treatment.
Yes 相关蛋白 (YAP) 已被证实对多种肿瘤的生长起着至关重要的作用。YAP 的丝氨酸 127 位的磷酸化会导致 YAP 转位到细胞核的抑制，从而不能调控诱导细胞增殖的靶基因的表达。YAP 定位或表达的化学操控可能为癌症治疗提供一种有效的方法。在 Bao 等人最近发表的一篇工作(J. Biochem. 2011;150:199-208)中，通过监测稳定表达绿色荧光蛋白标记的 YAP 的人骨肉瘤细胞中的 GFP-YAP 的亚细胞定位，筛选了各种化合物。通过这种基于细胞的测定，他们发现，β-肾上腺素能受体激动剂多巴酚丁胺通过抑制其核易位来减弱 YAP 依赖性转录。作者认为多巴酚丁胺可能是一种治疗癌症的药物。
