A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes
A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes
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DOI：
10.1038/sj.emboj.7601338
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发表时间：
2006-10-04
期刊：
影响因子：
11.4
通讯作者：
Murata, Shigeo
中科院分区：
文献类型：
--
作者：
Hamazaki, Jun;Iemura, Shun-ichiro;Murata, Shigeo
26S蛋白酶体是真核细胞中的一种多亚基蛋白水解酶。它由一个催化的20S蛋白酶体和两个附着在20S蛋白酶体两端的19S调节颗粒组成。在这里，我们描述了Adrm1作为一种新的蛋白酶体相互作用蛋白在哺乳动物细胞中的鉴定。虽然Adrm1的整个序列与酵母Rpn13有微弱的同源性，但氨基和羧基末端区域显示出显著的同源性。因此，我们将其命名为hRpn13。HRpn13通过其氨基末端与碱基Rpn2相互作用。大多数26S蛋白酶体含有hRpn13，但部分不含，表明hRpn13不是一个完整的亚基。有趣的是，我们发现hRpn13招募了UCH37，一种已知与26个蛋白酶体相关的去泛素酶。含有hRpn13和UCH37的KEKE基序的羧基末端区域参与了它们的物理相互作用。HRpn13基因敲除后，26S蛋白酶体的UCH37蛋白丢失，去泛素化活性降低，但没有引起明显的蛋白降解缺陷。我们的结果表明，hRpn13对UCH37的活性是必不可少的。
The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. It is composed of one catalytic 20S proteasome and two 19S regulatory particles attached on both ends of 20S proteasomes. Here, we describe the identification of Adrm1 as a novel proteasome interacting protein in mammalian cells. Although the overall sequence of Adrm1 has weak homology with the yeast Rpn13, the amino- and carboxyl-terminal regions exhibit significant homology. Therefore, we designated it as hRpn13. hRpn13 interacts with a base subunit Rpn2 via its amino-terminus. The majority of 26S proteasomes contain hRpn13, but a portion of them does not, indicating that hRpn13 is not an integral subunit. Intriguingly, we found that hRpn13 recruits UCH37, a deubiquitinating enzyme known to associate with 26 proteasomes. The carboxyl-terminal regions containing KEKE motifs of both hRpn13 and UCH37 are involved in their physical interaction. Knockdown of hRpn13 caused no obvious proteolytic defect but loss of UCH37 proteins and decrease in deubiquitinating activity of 26S proteasomes. Our results indicate that hRpn13 is essential for the activity of UCH37.