In eukaryotes, the ubiquitin–proteasome system is an essential pathway for protein degradation and cellular homeostasis. 26S proteasomes concentrate in the nucleus of budding yeast Saccharomyces cerevisiae due to the essential import adaptor protein Sts1 and the karyopherin-α protein Srp1. Here, we show that Sts1 facilitates proteasome nuclear import by recruiting proteasomes to the karyopherin-α/β heterodimer. Following nuclear transport, the karyopherin proteins are likely separated from Sts1 through interaction with RanGTP in the nucleus. RanGTP-induced release of Sts1 from the karyopherin proteins initiates Sts1 proteasomal degradation in vitro. Sts1 undergoes karyopherin-mediated nuclear import in the absence of proteasome interaction, but Sts1 degradation in vivo is only observed when proteasomes successfully localize to the nucleus. Sts1 appears to function as a proteasome import factor during exponential growth only, as it is not found in proteasome storage granules (PSGs) during prolonged glucose starvation, nor does it appear to contribute to the rapid nuclear reimport of proteasomes following glucose refeeding and PSG dissipation. We propose that Sts1 acts as a single-turnover proteasome nuclear import factor by recruiting karyopherins for transport and undergoing subsequent RanGTP-initiated ubiquitin-independent proteasomal degradation in the nucleus.

在真核生物中，泛素-蛋白酶体系统是蛋白质降解和细胞稳态的重要途径。由于必需的输入衔接蛋白 Sts1 和核蛋白α蛋白 Srp1,26S 蛋白酶体集中在出芽酵母酿酒酵母的细胞核中。在这里，我们表明 Sts1 通过将蛋白酶体募集到核蛋白 α/β 异二聚体来促进蛋白酶体核输入。核转运后，核黄蛋白可能通过与细胞核中的 RanGTP 相互作用从 Sts1 中分离出来。RanGTP 诱导的 ss1 从 karyopherin 蛋白中释放，在体外启动 Sts1 蛋白酶体降解。Sts1 在没有蛋白酶体相互作用的情况下经历核蛋白介导的核输入，但只有当蛋白酶体成功定位到细胞核时，才能观察到体内 Sts1 降解。Sts1 似乎仅在指数生长期间作为蛋白酶体输入因子发挥作用，因为它在长时间葡萄糖饥饿期间不在蛋白酶体储存颗粒 （PSG） 中发现，它似乎也无助于葡萄糖再喂养和 PSG 消散后蛋白酶体的快速核再输入。我们提出 Sts1 通过募集核蛋白进行运输并在细胞核中经历随后的 RanGTP 启动的泛素非依赖性蛋白酶体降解，从而充当单周转蛋白酶体输入因子。