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酵母模型为癌症相关蛋白提供的新见解。

New insights into cancer-related proteins provided by the yeast model.

机构信息

REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, University of Porto, Portugal.

出版信息

FEBS J. 2012 Mar;279(5):697-712. doi: 10.1111/j.1742-4658.2012.08477.x. Epub 2012 Feb 10.

Abstract

Cancer is a devastating disease with a profound impact on society. In recent years, yeast has provided a valuable contribution with respect to uncovering the molecular mechanisms underlying this disease, allowing the identification of new targets and novel therapeutic opportunities. Indeed, several attributes make yeast an ideal model system for the study of human diseases. It combines a high level of conservation between its cellular processes and those of mammalian cells, with advantages such as a short generation time, ease of genetic manipulation and a wealth of experimental tools for genome- and proteome-wide analyses. Additionally, the heterologous expression of disease-causing proteins in yeast has been successfully used to gain an understanding of the functions of these proteins and also to provide clues about the mechanisms of disease progression. Yeast research performed in recent years has demonstrated the tremendous potential of this model system, especially with the validation of findings obtained with yeast in more physiologically relevant models. The present review covers the major aspects of the most recent developments in the yeast research area with respect to cancer. It summarizes our current knowledge on yeast as a cellular model for investigating the molecular mechanisms of action of the major cancer-related proteins that, even without yeast orthologues, still recapitulate in yeast some of the key aspects of this cellular pathology. Moreover, the most recent contributions of yeast genetics and high-throughput screening technologies that aim to identify some of the potential causes underpinning this disorder, as well as discover new therapeutic agents, are discussed.

摘要

癌症是一种具有深远社会影响的毁灭性疾病。近年来,酵母在揭示这种疾病的分子机制方面做出了宝贵的贡献,为鉴定新靶点和新的治疗机会提供了可能。事实上,酵母有几个特点使其成为研究人类疾病的理想模型系统。它的细胞过程与哺乳动物细胞之间具有高度的保守性,同时还具有一些优势,例如较短的世代时间、易于遗传操作以及用于全基因组和蛋白质组分析的丰富实验工具。此外,在酵母中异源表达致病蛋白已成功用于了解这些蛋白的功能,并为疾病进展机制提供线索。近年来进行的酵母研究证明了这种模型系统的巨大潜力,特别是当在更具生理相关性的模型中验证了从酵母中获得的发现时。本文综述了近年来酵母研究领域在癌症方面的主要进展,总结了我们目前对酵母作为研究与癌症相关的主要蛋白的作用分子机制的细胞模型的认识,即使没有酵母的同源物,酵母仍能重现这种细胞病理学的一些关键方面。此外,还讨论了酵母遗传学和高通量筛选技术的最新进展,这些技术旨在确定这种疾病的一些潜在原因,并发现新的治疗药物。

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