通过蛋白质-蛋白质相互作用和遗传网络揭示的SUMO功能全球图谱。

Global map of SUMO function revealed by protein-protein interaction and genetic networks.

作者信息

Makhnevych Taras, Sydorskyy Yaroslav, Xin Xiaofeng, Srikumar Tharan, Vizeacoumar Franco J, Jeram Stanley M, Li Zhijian, Bahr Sondra, Andrews Brenda J, Boone Charles, Raught Brian

机构信息

Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S3E1, Canada.

出版信息

Mol Cell. 2009 Jan 16;33(1):124-35. doi: 10.1016/j.molcel.2008.12.025.

DOI:10.1016/j.molcel.2008.12.025

PMID:19150434

Abstract

Systematic functional genomics approaches were used to map a network centered on the small ubiquitin-related modifier (SUMO) system. Over 250 physical interactions were identified using the SUMO protein as bait in affinity purification-mass spectrometry and yeast two-hybrid screens. More than 500 genes and 1400 synthetic genetic interactions were mapped by synthetic genetic array (SGA) analysis using eight different SUMO pathway query genes. The resultant global SUMO network highlights its role in 15 major biological processes and better defines functional relationships between the different components of the SUMO pathway. Using this information-rich resource, we have identified roles for the SUMO system in the function of the AAA ATPase Cdc48p, the regulation of lipid metabolism, localization of the ATP-dependent endonuclease Dna2p, and recovery from the DNA-damage checkpoint.

摘要

系统功能基因组学方法被用于绘制一个以小泛素相关修饰物（SUMO）系统为中心的网络。在亲和纯化-质谱分析和酵母双杂交筛选中，以SUMO蛋白作为诱饵，鉴定出了超过250种物理相互作用。使用八个不同的SUMO途径查询基因，通过合成遗传阵列（SGA）分析绘制了500多个基因和1400个合成遗传相互作用。由此产生的全局SUMO网络突出了其在15个主要生物学过程中的作用，并更好地定义了SUMO途径不同组分之间的功能关系。利用这一信息丰富的资源，我们确定了SUMO系统在AAA ATP酶Cdc48p的功能、脂质代谢调节、ATP依赖性核酸内切酶Dna2p的定位以及从DNA损伤检查点恢复中的作用。