Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 2012 Oct 5;287(41):34400-9. doi: 10.1074/jbc.M112.390294. Epub 2012 Aug 17.
The ubiquitin-proteasome system is the major pathway for selective protein degradation in eukaryotes. Despite extensive study of this system, the mechanisms by which proteasome function and cell growth are coordinated remain unclear. Here, we identify Spg5 as a novel component of the ubiquitin-proteasome system. Spg5 binds the regulatory particle of the proteasome and the base subassembly in particular, but it is excluded from mature proteasomes. The SPG5 gene is strongly induced in the stationary phase of budding yeast, and spg5Δ mutants show a progressive loss of viability under these conditions. Accordingly, during logarithmic growth, Spg5 appears largely dispensable for proteasome function, but during stationary phase the proteasomes of spg5Δ mutants show both structural and functional defects. This loss of proteasome function is reflected in the accumulation of oxidized proteins preferentially in stationary phase in spg5Δ mutants. Thus, Spg5 is a positive regulator of the proteasome that is critical for survival of cells that have ceased to proliferate due to nutrient limitation.
泛素-蛋白酶体系统是真核生物中选择性蛋白降解的主要途径。尽管对该系统进行了广泛的研究，但蛋白酶体功能和细胞生长如何协调的机制仍不清楚。在这里，我们鉴定出 Spg5 是泛素-蛋白酶体系统的一个新组件。Spg5 与蛋白酶体的调节颗粒，特别是基底亚基结合，但它被排除在成熟的蛋白酶体之外。SPG5 基因在出芽酵母的静止期被强烈诱导，并且 spg5Δ 突变体在这些条件下表现出逐渐丧失活力。因此，在对数生长期，Spg5 对蛋白酶体功能的需求似乎不大，但在静止期，spg5Δ 突变体的蛋白酶体显示出结构和功能缺陷。这种蛋白酶体功能的丧失反映在氧化蛋白的积累中，在 spg5Δ 突变体中，这些蛋白主要在静止期积累。因此，Spg5 是蛋白酶体的正调节剂，对于因营养限制而停止增殖的细胞的存活至关重要。
