The parkinsonism-associated protein FBXO7 cooperates with the BAG6 complex in proteasome function and controls the subcellular localization of the complex.
The parkinsonism-associated protein FBXO7 cooperates with the BAG6 complex in proteasome function and controls the subcellular localization of the complex.
复制标题
帕金森病相关蛋白 FBXO7 与 BAG6 复合物配合蛋白酶体功能并控制该复合物的亚细胞定位
DOI：
10.1042/bcj20201000
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Stegmüller J.
中科院分区：
文献类型：
--
作者：
Wang Q;Crnkovic V;Preisinger C;Stegmüller J.
蛋白酶体活性的调节对于细胞内稳态是必不可少的，并且蛋白酶体活性的缺陷与包括帕金森病在内的各种疾病有关。F-box蛋白FBXO 7与早发性帕金森综合征有关，并且先前已显示在蛋白酶体活性和组装中具有调节作用。在这里，我们报告了E3泛素连接酶FBXO 7-SCF（SKP 1，cullin-1，F-box蛋白）与BAG 6复合物的关联，BAG 6复合物由BAG 6，GET 4和UBL 4A亚基组成。我们确定了亚基GET 4作为FBXO 7的直接相互作用，我们表明，亚基GET 4和UBL 4A所需的适当的蛋白酶体活性。我们的研究结果表明FBXO 7变体与GET 4的结合减少，FBXO 7变体导致蛋白酶体活性降低。此外，我们发现GET 4是FBXO 7的非蛋白水解底物，在活性FBXO 7-SCF存在下GET 4与BAG 6的结合增强，并且BAG 6复合物的细胞质定位依赖于E3泛素连接酶活性。总之，我们的研究表明，帕金森病相关的FBXO 7与BAG 6复合物在蛋白酶体功能中合作，并决定了该复合物的亚细胞定位。
The regulation of proteasome activity is essential to cellular homeostasis and defects have been implicated in various disorders including Parkinson disease. The F-box protein FBXO7 has been implicated in early-onset parkinsonism and has previously been shown to have a regulatory role in proteasome activity and assembly. Here, we report the association of the E3 ubiquitin ligase FBXO7-SCF (SKP1, cullin-1, F-box protein) with the BAG6 complex, consisting of the subunits BAG6, GET4 and UBL4A. We identify the subunit GET4 as a direct interactor of FBXO7 and we show that the subunits GET4 and UBL4A are required for proper proteasome activity. Our findings demonstrate reduced binding of FBXO7 variants to GET4 and that FBXO7 variants bring about reduced proteasome activity. In addition, we find that GET4 is a non-proteolytic substrate of FBXO7, that binding of GET4 to BAG6 is enhanced in the presence of active FBXO7-SCF and that the cytoplasmic localization of the BAG6 complex is dependent on the E3 ubiquitin ligase activity. Taken together, our study shows that the parkinsonism-associated FBXO7 cooperates with the BAG6 complex in proteasome function and determines the subcellular localization of this complex.
登录
查看更多内容
影响因子：
16
作者：
Wang Q;Liu Y;Soetandyo N;Baek K;Hegde R;Ye Y
通讯作者：
Ye Y
影响因子：
56.9
作者：
XIA, ZG;DICKENS, M;GREENBERG, ME
通讯作者：
GREENBERG, ME
DOI：
10.1083/jcb.200908092
发表时间：
2010-08-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Minami R;Hayakawa A;Kagawa H;Yanagi Y;Yokosawa H;Kawahara H
通讯作者：
Kawahara H
影响因子：
64.5
作者：
Kaneko, Takeumi;Hamazaki, Jun;Murata, Shigeo
通讯作者：
Murata, Shigeo
影响因子：
64.8
作者：
Hirano, Y;Hendil, KB;Murata, S
通讯作者：
Murata, S