Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Scientific Park, Baldiri i Reixac 15-21, 08028 Barcelona, Spain.
Mol Cell. 2010 Jun 11;38(5):733-45. doi: 10.1016/j.molcel.2010.05.001.
The proteasome recognizes its substrates via a diverse set of ubiquitin receptors, including subunits Rpn10/S5a and Rpn13. In addition, shuttling factors, such as Rad23, recruit substrates to the proteasome by delivering ubiquitinated proteins. Despite the increasing understanding of the factors involved in this process, the regulation of substrate delivery remains largely unexplored. Here we report that Rpn10 is monoubiquitinated in vivo and that this modification has profound effects on proteasome function. Monoubiquitination regulates the capacity of Rpn10 to interact with substrates by inhibiting Rpn10's ubiquitin-interacting motif (UIM). We show that Rsp5, a member of NEDD4 ubiquitin-protein ligase family, and Ubp2, a deubiquitinating enzyme, control the levels of Rpn10 monoubiquitination in vivo. Notably, monoubiquitination of Rpn10 is decreased under stress conditions, suggesting a mechanism of control of receptor availability mediated by the Rsp5-Ubp2 system. Our results reveal an unanticipated link between monoubiquitination signal and regulation of proteasome function.
蛋白酶体通过一系列不同的泛素受体识别其底物，包括 Rpn10/S5a 和 Rpn13 亚基。此外，穿梭因子，如 Rad23，通过将泛素化蛋白递送给蛋白酶体来招募底物。尽管人们对参与这一过程的因素有了越来越多的了解，但底物传递的调节在很大程度上仍未得到探索。在这里，我们报告 Rpn10 在体内被单泛素化，这种修饰对蛋白酶体功能有深远的影响。单泛素化通过抑制 Rpn10 的泛素相互作用基序 (UIM) 调节 Rpn10 与底物相互作用的能力。我们表明，NEDD4 泛素蛋白连接酶家族的成员 Rsp5 和去泛素化酶 Ubp2 在体内控制 Rpn10 单泛素化的水平。值得注意的是，Rpn10 的单泛素化在应激条件下减少，这表明 Rsp5-Ubp2 系统介导的受体可用性控制的一种机制。我们的结果揭示了单泛素化信号与蛋白酶体功能调节之间的意外联系。
