Protein aggregation is mostly viewed as deleterious and irreversible causing several pathologies. However, reversible protein aggregation has recently emerged as a novel concept for cellular regulation. Here, we characterize stress-induced, reversible aggregation of yeast pyruvate kinase, Cdc19. Aggregation of Cdc19 is regulated by oligomerization and binding to allosteric regulators. We identify a region of low compositional complexity (LCR) within Cdc19 as necessary and sufficient for reversible aggregation. During exponential growth, shielding the LCR within tetrameric Cdc19 or phosphorylation of the LCR prevents unscheduled aggregation, while its dephosphorylation is necessary for reversible aggregation during stress. Cdc19 aggregation triggers its localization to stress granules and modulates their formation and dissolution. Reversible aggregation protects Cdc19 from stress-induced degradation, thereby allowing cell cycle restart after stress. Several other enzymes necessary for G1 progression also contain LCRs and aggregate reversibly during stress, implying that reversible aggregation represents a conserved mechanism regulating cell growth and survival.

中文翻译：

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可逆的蛋白质聚集是确保应激后细胞周期重启的保​​护机制

蛋白质聚集通常被认为是有害的和不可逆的，引起多种病理。然而，最近可逆的蛋白质聚集已经成为细胞调节的新概念。在这里，我们表征酵母丙酮酸激酶，Cdc19的应力诱导的，可逆的聚集。Cdc19的聚集通过寡聚化和与变构调节剂的结合来调节。我们在Cdc19中确定了一个低组成复杂度（LCR）的区域，该区域对于可逆聚合而言是必要且足够的。在指数增长期间，将LCR屏蔽在四聚体Cdc19内或LCR的磷酸化可防止计划外的聚集，而其去磷酸化则是应激期间可逆聚集所必需的。Cdc19聚集触发其定位到应力颗粒并调节其形成和溶解。可逆聚集可保护Cdc19免受应激诱导的降解，从而使细胞周期在应激后重启。G1进程所必需的其他几种酶也包含LCR，并且在应激过程中可逆地聚集，这表明可逆聚集代表了调节细胞生长和存活的保守机制。