Kau Tweeny R, Silver Pamela A
Dept of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Dept of Cancer Biology, The Dana Farber Cancer Institute, Boston, MA 02115, USA.
Drug Discov Today. 2003 Jan 15;8(2):78-85. doi: 10.1016/s1359-6446(02)02562-x.
The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a potential therapeutic target, only two nuclear transport inhibitors have been reported. Here, we explore the roles of small-molecule inhibitors that cause target proteins to sequester in either the nucleus or cytoplasm. Methods of artificially targeting proteins to the nucleus or cytoplasm using peptide aptamer technology are also discussed.
许多参与细胞生长的关键蛋白质和转录因子的功能可通过其细胞定位来调节。这类蛋白质包括肿瘤抑制因子p53和核因子κB。尽管将这类蛋白质困在细胞核或细胞质中的想法已作为一种潜在的治疗靶点被提出，但据报道仅有两种核转运抑制剂。在此，我们探究使靶蛋白在细胞核或细胞质中隔离的小分子抑制剂的作用。还讨论了利用肽适配体技术将蛋白质人工靶向细胞核或细胞质的方法。
