Hop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced proteasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70-Hsp90 complex, which can also be demonstrated in vitro, compensates for the proteasomal defect and ensures the proteostatic equilibrium. Thus, cells may act on the level and/or activity of Hop to shift the proteostatic balance between folding and degradation.

Hop / Stip1 / Sti1被认为是必不可少的辅助伴侣，以促进Hsp70和Hsp90分子伴侣之间的底物转移。尽管提出了蛋白质折叠和成熟的关键功能，但在许多真核生物中它并不是必不可少的，细菌缺乏直系同源物。我们着手确定和表征其真核生物特有的功能。人类细胞系和具有Hop / Sti1基因缺失的发芽酵母显示蛋白酶体活性降低，这是由于核心颗粒被调控颗粒覆盖不足所致。出乎意料的是，敲除细胞在防止蛋白质聚集和促进蛋白质重折叠方面更熟练。在不受Hop约束的情况下，原核生物样Hsp70-Hsp90复合物的更有效折叠活性也可以在体外得到证实，补偿蛋白酶体缺陷并确保蛋白平衡。因此，细胞可以在Hop的水平和/或活性上起作用，以在折叠和降解之间改变蛋白静态平衡。