Intracellular protein inclusions are diverse cellular entities with distinct biological properties. They vary in their protein content, sequestration sites, physiological function, conditions for their generation, and turnover rates. Major distinctions have been recognized between stationary amyloids and dynamic, misfolded protein deposits. The former being a dead end for irreversibly misfolded proteins, hence, cleared predominantly by autophagy, while the latter consists of a protein-quality control mechanism, important for cell endurance, where proteins are sequestered during proteotoxic stress and resolved upon its relief. Accordingly, the disaggregation of transient inclusions is a regulated process consisting of protein solubilization, followed by a triage step to either refolding or to ubiquitin-mediated degradation. Recent studies have demonstrated an indispensable role in disaggregation for components of the chaperone and the ubiquitin–proteasome systems. These include heat-shock chaperones of the 40/70/100 kDa families, the proteasome, proteasome substrate shuttling factors, and deubiquitylating enzymes. Thus, a functional link has been established between the chaperone machinery that extracts proteins from transient deposits and 26S proteasome-dependent disaggregation, indicative of a coordinated process. In this review, we discuss data emanating from these important studies and subsequently consolidate the information in the form of a working model for the disaggregation mechanism.

中文翻译：

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解除锁定：遍在蛋白包涵体分解中泛素-蛋白酶体系统的新兴角色。

细胞内蛋白质包裹体是具有不同生物学特性的多种细胞实体。它们的蛋白质含量，螯合位点，生理功能，生成条件和周转率各不相同。已经认识到固定淀粉样蛋白与动态错误折叠的蛋白质沉积物之间的主要区别。前者是不可逆错误折叠的蛋白质的死胡同，因此主要通过自噬清除，而后者则由蛋白质质量控​​制机制组成，这对于细胞的耐力很重要，在蛋白质毒性应激期间，蛋白质被隔离并在其释放时被分解。因此，瞬态夹杂物的分解是一个受调节的过程，由蛋白质溶解，紧接着的重新分类或遍在蛋白介导的降解的分类步骤组成。最近的研究表明，在分子伴侣和泛素-蛋白酶体系统各组分的分解中起着不可或缺的作用。这些包括40/70/100 kDa家族的热休克分子伴侣，蛋白酶体，蛋白酶体底物穿梭因子和去泛素化酶。因此，已经建立了从瞬时沉积物中提取蛋白质的分子伴侣机制与26S蛋白酶体依赖性分解之间的功能联系，这表明了协调的过程。在这篇综述中，我们讨论了来自这些重要研究的数据，随后将这些信息以一种用于分解机制的工作模型的形式进行了整合。这些包括40/70/100 kDa家族的热休克分子伴侣，蛋白酶体，蛋白酶体底物穿梭因子和去泛素化酶。因此，已经建立了从瞬时沉积物中提取蛋白质的分子伴侣机制与26S蛋白酶体依赖性分解之间的功能联系，这表明了协调的过程。在这篇综述中，我们讨论了来自这些重要研究的数据，随后将这些信息以一种用于分解机制的工作模型的形式进行了整合。这些包括40/70/100 kDa家族的热休克分子伴侣，蛋白酶体，蛋白酶体底物穿梭因子和去泛素化酶。因此，已经建立了从瞬时沉积物中提取蛋白质的分子伴侣机制与26S蛋白酶体依赖性分解之间的功能联系，这表明了协调的过程。在这篇综述中，我们讨论了来自这些重要研究的数据，随后将这些信息以一种用于分解机制的工作模型的形式进行了整合。