The Ubiquitin-Proteasome System Is a Key Component of the SUMO-2/3 Cycle
The Ubiquitin-Proteasome System Is a Key Component of the SUMO-2/3 Cycle
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DOI：
10.1074/mcp.m800025-mcp200
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发表时间：
2008-11-01
影响因子：
7
通讯作者：
Vertegaal, Alfred C. O.
中科院分区：
文献类型：
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作者：
Schimmel, Joost;Larsen, Katja M.;Vertegaal, Alfred C. O.
许多蛋白质受到各种翻译后修饰的调节，并且通常需要协调这些修饰才能完全控制活性。目前，人们对不同翻译后修饰的组合活性知之甚少。在这里，我们表明苏酰化和泛素化之间存在广泛的串扰。我们发现 SUMO-2 结合蛋白的一个子集随后被蛋白酶体泛素化和降解。在筛选优先 SUMO-1 或 SUMO-2 靶蛋白时，我们发现泛素在纯化的 SUMO-2 缀合物中积累，但不在 SUMO-1 缀合物中积累。抑制蛋白酶体后，纯化的 SUMO-2 缀合物中泛素的量增加。此外，我们发现内源性 SUMO-2/3 缀合物（而非内源性 SUMO-1 缀合物）响应蛋白酶体抑制剂而积累。定量蛋白质组学实验能够鉴定出 73 种 SUMO-2 缀合蛋白，这些蛋白在用蛋白酶体抑制剂处理的细胞中积累。 SUMO-2/3 和泛素蛋白酶体系统之间的串扰控制着许多调节核酸代谢各个方面的靶蛋白。令人惊讶的是，蛋白酶体抑制剂降低了 40 种 SUMO-2 缀合蛋白的相对丰度，这可能是由于缺乏回收的 SUMO-2。我们得出结论，SUMO-2/3 缀合和泛素-蛋白酶体系统紧密结合并以合作方式发挥作用。分子与细胞蛋白质组学 7：2107-2122，2008。
Many proteins are regulated by a variety of post-translational modifications, and orchestration of these modifications is frequently required for full control of activity. Currently little is known about the combinatorial activity of different post-translational modifications. Here we show that extensive cross-talk exists between sumoylation and ubiquitination. We found that a subset of SUMO-2-conjugated proteins is subsequently ubiquitinated and degraded by the proteasome. In a screen for preferential SUMO-1 or SUMO-2 target proteins, we found that ubiquitin accumulated in purified SUMO-2 conjugates but not in SUMO-1 conjugates. Upon inhibition of the proteasome, the amount of ubiquitin in purified SUMO-2 conjugates increased. In addition, we found that endogenous SUMO-2/3 conjugates, but not endogenous SUMO-1 conjugates, accumulated in response to proteasome inhibitors. Quantitative proteomics experiments enabled the identification of 73 SUMO-2-conjugated proteins that accumulated in cells treated with proteasome inhibitors. Cross-talk between SUMO-2/3 and the ubiquitin-proteasome system controls many target proteins that regulate all aspects of nucleic acid metabolism. Surprisingly the relative abundance of 40 SUMO-2-conjugated proteins was reduced by proteasome inhibitors possibly because of a lack of recycled SUMO-2. We conclude that SUMO-2/3 conjugation and the ubiquitin-proteasome system are tightly integrated and act in a cooperative manner. Molecular & Cellular Proteomics 7: 2107-2122, 2008.