System-Wide Changes to SUMO Modifications in Response to Heat Shock

System-Wide Changes to SUMO Modifications in Response to Heat Shock
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DOI:
10.1126/scisignal.2000282
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发表时间:
2009-05-26
期刊:
影响因子:
7.3
通讯作者:
Hay, Ronald T.
Hay, Ronald T.
中科院分区:
生物学1区
文献类型:
--
作者:
Golebiowski, Filip;Matic, Ivan;Hay, Ronald T.

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小泛素样修饰物(SUMO)蛋白与靶蛋白的共价结合调节许多重要的真核细胞机制。虽然SUMO蛋白质结合的分子结果是相对较好的理解,很少有人知道的细胞信号,调节其底物的修饰。在这里,我们表明SUMO-2和SUMO-3是细胞在热休克中存活所必需的。通过定量标记技术、SUMO化蛋白的严格纯化、先进的质谱技术和新的数据分析技术,我们对766种假定底物的SUMO化状态的热休克诱导变化进行了定量。在热休克反应中,SUMO聚合成polySUMO链,并在广泛的蛋白质中重新分布,这些蛋白质参与细胞周期调控;凋亡;蛋白质的运输、折叠和降解;转录;翻译;以及DNA复制、重组和修复。这种全面的蛋白质组学分析的底物的泛素样修饰剂(Ubl)确定了一个普遍的作用SUMO蛋白在生物反应高温应激。
Covalent conjugation of the small ubiquitin-like modifier (SUMO) proteins to target proteins regulates many important eukaryotic cellular mechanisms. Although the molecular consequences of the conjugation of SUMO proteins are relatively well understood, little is known about the cellular signals that regulate the modification of their substrates. Here, we show that SUMO-2 and SUMO-3 are required for cells to survive heat shock. Through quantitative labeling techniques, stringent purification of SUMOylated proteins, advanced mass spectrometric technology, and novel techniques of data analysis, we quantified heat shock-induced changes in the SUMOylation state of 766 putative substrates. In response to heat shock, SUMO was polymerized into polySUMO chains and redistributed among a wide range of proteins involved in cell cycle regulation; apoptosis; the trafficking, folding, and degradation of proteins; transcription; translation; and DNA replication, recombination, and repair. This comprehensive proteomic analysis of the substrates of a ubiquitin-like modifier (Ubl) identifies a pervasive role for SUMO proteins in the biologic response to hyperthermic stress.