In eukaryotic cells, half of all proteins function as subunits within multiprotein complexes. Imbalanced synthesis of subunits leads to unassembled intermediates that must be degraded to minimize cellular toxicity. Here, we found that excess PSMC5, a subunit of the proteasome base, was targeted for degradation by the HERC1 ubiquitin ligase in mammalian cells. HERC1 identified unassembled PSMC5 by its cognate assembly chaperone PAAF1. Because PAAF1 only dissociates after assembly, HERC1 could also engage later assembly intermediates such as the PSMC4-PSMC5-PAAF1 complex. A missense mutant of HERC1 that causes neurodegeneration in mice was impaired in the recognition and ubiquitination of the PSMC5-PAAF1 complex. Thus, proteasome assembly factors can serve as adaptors for ubiquitin ligases to facilitate elimination of unassembled intermediates and maintain protein homeostasis.

在真核细胞中，一半的蛋白质作为多蛋白复合物中的亚基发挥作用。亚基的不平衡合成导致未组装的中间体必须被降解以最小化细胞毒性。在这里，我们发现多余的 PSMC5（蛋白酶体碱基的一个亚基）被哺乳动物细胞中的 HERC1 泛素连接酶降解。HERC1 通过其同源组装伴侣 PAAF1 识别未组装的 PSMC5。由于 PAAF1 仅在组装后解离，因此 HERC1 还可以参与后期组装中间体，例如 PSMC4-PSMC5-PAAF1 复合物。导致小鼠神经变性的 HERC1 错义突变体在 PSMC5-PAAF1 复合物的识别和泛素化方面受损。因此，