Autoregulation of the 26S proteasome by in situ ubiquitination.
Autoregulation of the 26S proteasome by in situ ubiquitination.
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DOI：
10.1091/mbc.e13-10-0585
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发表时间：
2014-06-15
影响因子：
3.3
通讯作者：
Liu CW
中科院分区：
文献类型：
--
作者：
Jacobson AD;MacFadden A;Wu Z;Peng J;Liu CW
26S蛋白酶体被蛋白酶体相关的泛素化酶泛素化。蛋白酶体泛素化损害蛋白酶体降解，并受去泛素化、底物结合和细胞应激的调节。有人提出，在原位泛素化自动调节细胞中的蛋白酶体活性。26S蛋白酶体降解泛素化蛋白，蛋白酶体降解控制各种细胞事件。在这里，我们报告说，人类26 S蛋白酶体是泛素化的，其中泛素受体Adrm1和S5a，ATP酶亚基Rpt5，和去泛素化酶Uch37是泛素化原位蛋白酶体相关的泛素化酶。这些亚基的泛素化显著损害了26S蛋白酶体结合、去泛素化和降解泛素化蛋白的能力。此外，26 S蛋白酶体的泛素化可以被蛋白酶体驻留的去泛素化酶、多聚泛素链的结合和某些细胞应激所拮抗，表明蛋白酶体泛素化在细胞中是动态的和受调节的。我们认为26S蛋白酶体的原位泛素化调节其活性，其功能可能是调节蛋白酶体活性以响应细胞泛素化水平的改变。
The 26S proteasome is ubiquitinated by proteasome-associating ubiquitination enzymes. Proteasome ubiquitination impairs proteasomal degradation and is regulated by deubiquitination, substrate binding, and cellular stress. It is proposed that in situ ubiquitination autoregulates proteasomal activity in cells. The 26S proteasome degrades ubiquitinated proteins, and proteasomal degradation controls various cellular events. Here we report that the human 26S proteasome is ubiquitinated, by which the ubiquitin receptors Adrm1 and S5a, the ATPase subunit Rpt5, and the deubiquitinating enzyme Uch37 are ubiquitinated in situ by proteasome-associating ubiquitination enzymes. Ubiquitination of these subunits significantly impairs the 26S proteasome's ability to bind, deubiquitinate, and degrade ubiquitinated proteins. Moreover, ubiquitination of the 26S proteasome can be antagonized by proteasome-residing deubiquitinating enzymes, by the binding of polyubiquitin chains, and by certain cellular stress, indicating that proteasome ubiquitination is dynamic and regulated in cells. We propose that in situ ubiquitination of the 26S proteasome regulates its activity, which could function to adjust proteasomal activity in response to the alteration of cellular ubiquitination levels.