Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, Spain.
Institut Jacques Monod, Centre National de la Recherche Scientifique, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
J Biol Chem. 2013 Jun 7;288(23):16206-16211. doi: 10.1074/jbc.C113.452250. Epub 2013 May 3.
The length of the ubiquitin chain on a substrate dictates various functional outcomes, yet little is known about its regulation in vivo. The yeast arrestin-related protein Rim8/Art9 is monoubiquitinated in vivo by the Rsp5 ubiquitin ligase. This also requires Vps23, a protein that displays an ubiquitin-E2 variant (UEV) domain. Here, we report that binding of the UEV domain to Rim8 interferes with ubiquitin chain elongation and directs Rim8 monoubiquitination. We propose that Vps23 UEV competes with Rsp5 HECT N-lobe for binding to the first conjugated ubiquitin, thereby preventing polyubiquitination. These findings reveal a novel mechanism to control ubiquitin chain length on substrates in vivo.
底物上泛素链的长度决定了各种功能结果，但体内对其调控知之甚少。酵母抑制素相关蛋白 Rim8/Art9 被 Rsp5 泛素连接酶在体内单泛素化。这还需要 Vps23，一种具有泛素-E2 变体 (UEV) 结构域的蛋白质。在这里，我们报告说，UEV 结构域与 Rim8 的结合会干扰泛素链的延伸，并指导 Rim8 的单泛素化。我们提出，Vps23 UEV 与 Rsp5 HECT N 结构域竞争结合第一个连接的泛素，从而防止多泛素化。这些发现揭示了一种控制体内底物上泛素链长度的新机制。
