Interplay of Posttranslational Modifications in Sp1 Mediates Sp1 Stability during Cell Cycle Progression
Interplay of Posttranslational Modifications in Sp1 Mediates Sp1 Stability during Cell Cycle Progression
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DOI：
10.1016/j.jmb.2011.09.027
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发表时间：
2011-11-18
影响因子：
5.6
通讯作者：
Hung, Jan-Jong
中科院分区：
文献类型：
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作者：
Wang, Yi-Ting;Yang, Wen-Bin;Hung, Jan-Jong
尽管已知SP1经历了翻译后修饰，例如磷酸化，糖基化，乙酰化，Sumoylation和泛素化，但对于可能影响其整体水平的不同形式的SP1之间可能的相互作用知之甚少。 SP1水平的变化是否影响任何生物细胞过程，也尚不清楚。在这里，我们将RNF4确定为SP1的泛素E3连接酶。从体外和体内实验中，我们发现sumoyy的SP1可以将RNF4募集为泛素E3连接酶，可将Sumoylelsp1的sp1受到蛋白酶体降解。 SPL映射显示了两个与泛素化相关的结构域：SP1的N末端（Lys16）和SP1的C端在与RNF4直接相互作用的C-末端中的一个小型泛素样修饰符。有趣的是，当Sp1在有丝分裂期间通过C-Jun NH2-末端激酶1在THR739处磷酸化时，这种SP1的磷酸化形式消除了SP1-RNF4相互作用。我们的结果表明，虽然Sumoyy的SP1受到蛋白酶体降解的影响，但在细胞周期期间发生的磷酸化可以通过抑制SP1-RNF4相互作用来保护SP1免受降解。因此，我们提出，SP1翻译后修饰之间的相互作用在细胞周期进程中起重要作用，并使SP1保持有丝分裂的临界水平。 （c）2011 Elsevier Ltd.保留所有权利。
Although Sp1 is known to undergo posttranslational modifications such as phosphorylation, glycosylation, acetylation, sumoylation, and ubiquitination, little is known about the possible interplay between the different forms of Sp1 that may affect its overall levels. It is also unknown whether changes in the levels of Sp1 influence any biological cell processes. Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation. Spl mapping revealed two ubiquitination-related domains: a small ubiquitin-like modifier in the N-terminus of Sp1(Lys16) and the C-terminus of Sp1 that directly interacts with RNF4. Interestingly, when Sp1 was phosphorylated at Thr739 by c-Jun NH2-terminal kinase 1 during mitosis, this phosphorylated form of Sp1 abolished the Sp1-RNF4 interaction. Our results show that, while sumoylated Sp1 subjects to proteasomal degradation, the phosphorylation that occurs during the cell cycle can protect Sp1 from degradation by repressing the Sp1-RNF4 interaction. Thus, we propose that the interplay between posttranslational modifications of Sp1 plays an important role in cell cycle progression and keeps Sp1 at a critical level for mitosis. (C) 2011 Elsevier Ltd. All rights reserved.