Tu William B, Helander Sara, Pilstål Robert, Hickman K Ashley, Lourenco Corey, Jurisica Igor, Raught Brian, Wallner Björn, Sunnerhagen Maria, Penn Linda Z
Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
Biochim Biophys Acta. 2015 May;1849(5):469-83. doi: 10.1016/j.bbagrm.2014.06.002. Epub 2014 Jun 14.
The Myc oncoprotein is a key contributor to the development of many human cancers. As such, understanding its molecular activities and biological functions has been a field of active research since its discovery more than three decades ago. Genome-wide studies have revealed Myc to be a global regulator of gene expression. The identification of its DNA-binding partner protein, Max, launched an area of extensive research into both the protein-protein interactions and protein structure of Myc. In this review, we highlight key insights with respect to Myc interactors and protein structure that contribute to the understanding of Myc's roles in transcriptional regulation and cancer. Structural analyses of Myc show many critical regions with transient structures that mediate protein interactions and biological functions. Interactors, such as Max, TRRAP, and PTEF-b, provide mechanistic insight into Myc's transcriptional activities, while others, such as ubiquitin ligases, regulate the Myc protein itself. It is appreciated that Myc possesses a large interactome, yet the functional relevance of many interactors remains unknown. Here, we discuss future research trends that embrace advances in genome-wide and proteome-wide approaches to systematically elucidate mechanisms of Myc action. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
Myc癌蛋白是许多人类癌症发生发展的关键因素。因此，自三十多年前被发现以来，了解其分子活性和生物学功能一直是一个活跃的研究领域。全基因组研究表明Myc是基因表达的全局调节因子。其DNA结合伴侣蛋白Max的鉴定开启了对Myc的蛋白质-蛋白质相互作用和蛋白质结构的广泛研究。在这篇综述中，我们着重介绍了关于Myc相互作用蛋白和蛋白质结构的关键见解，这些见解有助于理解Myc在转录调控和癌症中的作用。对Myc的结构分析显示了许多具有瞬时结构的关键区域，这些区域介导蛋白质相互作用和生物学功能。相互作用蛋白，如Max、TRRAP和P-TEFb，为Myc的转录活性提供了机制性见解，而其他蛋白，如泛素连接酶，则调节Myc蛋白本身。人们认识到Myc拥有一个庞大的相互作用组，但许多相互作用蛋白的功能相关性仍然未知。在这里，我们讨论了未来的研究趋势，这些趋势涵盖了全基因组和蛋白质组方法的进展，以系统地阐明Myc作用的机制。本文是名为“细胞生物学和病理学中的Myc蛋白”的特刊的一部分。
