Protein moonlighting: a new factor in biology and medicine
Protein moonlighting: a new factor in biology and medicine
复制标题
DOI：
10.1042/bst20140273
复制
发表时间：
2014-12-01
影响因子：
3.9
通讯作者：
Martin, Andrew C. R.
中科院分区：
文献类型：
--
作者：
Henderson, Brian;Martin, Andrew C. R.
蛋白质兼职现象是在20世纪80年代和90年代发现的，目前对兼职蛋白质的定义是在20世纪90年代末提供的。从那时起，在生命的所有三个领域中已经鉴定出数百种兼职蛋白质，并且随着蛋白质兼职在生物学和医学中的重要性变得明显，发现的速度正在加快。最近对人类基因组中蛋白质编码基因数量（约19000个）的重新评估是相信蛋白质兼职可能是一种比目前兼职蛋白质数量更普遍的现象的原因之一，并且对兼职蛋白质比例的初步研究将同意这一假设。蛋白质兼职可能是解释人类基因组中编码的蛋白质数量看似很少的一种方式。兼职蛋白质具有新的生物学功能，从而扩展了人类功能蛋白质组的范围。迄今为止发现的数百种兼职蛋白质在生物学的许多方面发挥着重要作用。例如，甘油醛-3-磷酸脱氢酶（GAPDH）、热休克蛋白60（Hsp 60）和tRNA合成酶在真核细胞中发挥广泛的生物学作用，并且越来越多的真核兼职蛋白被认为在生理过程中发挥重要作用，例如精子获能、植入、妊娠中的免疫调节、血液凝固、血管再生和炎症控制。蛋白质兼职的黑暗面发现了一系列兼职蛋白质在各种人类疾病中发挥作用，包括癌症，心血管疾病，艾滋病毒和囊性纤维化。然而，一些兼职蛋白正在测试其治疗潜力，包括免疫球蛋白重链结合蛋白（BiP），用于类风湿性关节炎，和Hsp 90用于伤口愈合。此外，在过去的20年中，已经出现了大量的细菌兼职蛋白作为毒力因子在细菌-宿主相互作用中发挥重要作用，因此是细菌感染的潜在治疗靶点。因此，随着我们在21世纪的进步，兼职蛋白质可能会在生物学和医学中发挥越来越重要的作用。希望一些主要的未回答的问题，如蛋白质兼职的进化机制，兼职蛋白质的结构生物学及其在细胞系统的系统生物学中的作用，可以在此期间得到解决。
The phenomenon of protein moonlighting was discovered in the 1980s and 1990s, and the current definition of what constitutes a moonlighting protein was provided at the end of the 1990s. Since this time, several hundred moonlighting proteins have been identified in all three domains of life, and the rate of discovery is accelerating as the importance of protein moonlighting in biology and medicine becomes apparent. The recent re-evaluation of the number of protein-coding genes in the human genome (approximately 19000) is one reason for believing that protein moonlighting may be a more general phenomenon than the current number of moonlighting proteins would suggest, and preliminary studies of the proportion of proteins that moonlight would concur with this hypothesis. Protein moonlighting could be one way of explaining the seemingly small number of proteins that are encoded in the human genome. It is emerging that moonlighting proteins can exhibit novel biological functions, thus extending the range of the human functional proteome. The several hundred moonlighting proteins so far discovered play important roles in many aspects of biology. For example, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), heat-shock protein 60 (Hsp60) and tRNA synthetases play a wide range of biological roles in eukaryotic cells, and a growing number of eukaryotic moonlighting proteins are recognized to play important roles in physiological processes such as sperm capacitation, implantation, immune regulation in pregnancy, blood coagulation, vascular regeneration and control of inflammation. The dark side of protein moonlighting finds a range of moonlighting proteins playing roles in various human diseases including cancer, cardiovascular disease, HIV and cystic fibrosis. However, some moonlighting proteins are being tested for their therapeutic potential, including immunoglobulin heavy-chain-binding protein (BiP), for rheumatoid arthritis, and Hsp90 for wound healing. In addition, it has emerged over the last 20 years that a large number of bacterial moonlighting proteins play important roles in bacteria-host interactions as virulence factors and are therefore potential therapeutic targets in bacterial infections. So as we progress in the 21st Century, it is likely that moonlighting proteins will be seen to play an increasingly important role in biology and medicine. It is hoped that some of the major unanswered questions, such as the mechanism of evolution of protein moonlighting, the structural biology of moonlighting proteins and their role in the systems biology of cellular systems can be addressed during this period.