Archer Chase T, Burdine Lyle, Liu Bo, Ferdous Anwarul, Johnston Stephen Albert, Kodadek Thomas
Division of Translational Research and Department of Internal Medicine, University of Texas-Southwestern Medical Center, Dallas, TX 75390-9185, USA.
J Biol Chem. 2008 Aug 1;283(31):21789-98. doi: 10.1074/jbc.M803075200. Epub 2008 May 30.
Destabilization of activator-DNA complexes by the proteasomal ATPases can inhibit transcription by limiting activator interaction with DNA. Modification of the activator by monoubiquitylation 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.
蛋白酶体ATP酶使激活剂与DNA复合物不稳定，可通过限制激活剂与DNA的相互作用来抑制转录。单泛素化修饰激活剂可保护激活剂免受这种去稳定化活性的影响。在本研究中，我们探究了单泛素化这种保护作用的机制。使用新型标记转移和化学交联技术，我们发现泛素直接与ATP酶复合物接触，显然是通过Rpn1和Rpt1。这种相互作用通过变构过程导致激活结构域-ATP酶复合物解离。我们提出了一个模型，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。
