Physical and functional interactions of monoubiquitylated transactivators with the proteasome
Physical and functional interactions of monoubiquitylated transactivators with the proteasome
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DOI：
10.1074/jbc.m803075200
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Kodadek, Thomas
中科院分区：
文献类型：
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作者：
Archer, Chase T.;Burdine, Lyle;Kodadek, Thomas
通过蛋白酶体ATP酶使激活剂-DNA复合物失稳可以通过限制激活剂与DNA的相互作用来抑制转录。活化剂通过单酰二喹啉化的修饰保护活化剂免受这种去稳定活性。在这项研究中，我们探讨了单泛素化的这种保护作用的机制。使用新的标签转移和化学交联技术，我们表明，泛素直接接触的ATP酶复合物，显然是通过Rpn 1和Rpt 1。这种相互作用导致活化结构域-ATP酶复合物通过变构过程解离。提出了一种模型，其中激活剂单泛素化用于限制激活剂-ATP酶复合物相互作用的寿命，从而限制ATP酶展开激活剂和解离蛋白质-DNA复合物的能力。
Destabilization of activator-DNA complexes by the proteasomal ATPases can inhibit transcription by limiting activator interaction with DNA. Modification of the activator by monou-biquitylation protects the activator from this destabilization activity. In this study, we probe the mechanism of this protective effect of monoubiquitylation. Using novel label transfer and chemical cross-linking techniques, we show that ubiquitin contacts the ATPase complex directly, apparently via Rpn1 and Rpt1. This interaction results in the dissociation of the activation domain-ATPase complex via an allosteric process. A model is proposed in which activator monoubiquitylation serves to limit the lifetime of the activator-ATPase complex interaction and thus the ability of the ATPases to unfold the activator and dissociate the protein-DNA complex.