The Saccharomyces cerevisiae ubiquitin-proteasome system
The Saccharomyces cerevisiae ubiquitin-proteasome system
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DOI：
10.1098/rstb.1999.0495
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发表时间：
1999-09-29
期刊：
影响因子：
--
通讯作者：
Connerly, PL
中科院分区：
文献类型：
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作者：
Hochstrasser, M;Johnson, PR;Connerly, PL
我们对酵母泛素-蛋白酶体途径的研究已经揭示了在这个复杂系统中控制底物选择性和蛋白水解的一些一般原则。大部分工作集中在破坏酵母转录因子MAT α 2上。α 2蛋白是多泛素化的，在α-单倍体细胞中迅速降解。蛋白水解靶向的一种途径，依赖于两种不同的内质网定位的泛素缀合酶，识别α 2中两亲性螺旋的疏水面。有趣的是，α 2和α 1同源结构域蛋白之间的异源二聚体形成阻断了α 2在α/α-二倍体细胞中的降解。这些数据表明，降解信号可能会重叠蛋白质-蛋白质相互作用表面，允许一个简单的空间机制调节降解。对α 2降解的分析导致了20 S和26 S蛋白酶体亚基的鉴定，随后发现了蛋白酶体组装和活性位点形成的几个关键特征。最后，已经清楚的是，蛋白质（聚）泛素化在体内是高度动态的，我们对酵母去泛素化酶的研究说明了这些酶如何促进不同底物的蛋白水解。
Our studies of the yeast ubiquitin-proteasome pathway have uncovered a number of general principles that govern substrate selectivity and proteolysis in this complex system. Much of the work has focused on the destruction of a yeast transcription factor, MAT alpha 2. The alpha 2 protein is polyubiquitinated and rapidly degraded in alpha-haploid cells. One pathway of proteolytic targeting, which depends on two distinct endoplasmic reticulum-localized ubiquitin-conjugating enzymes, recognizes the hydrophobic face of an amphipathic helix in alpha 2. Interestingly, degradation of alpha 2 is blocked in a/alpha-diploid cells by heterodimer formation between the alpha 2 and al homeodomain proteins. The data suggest that degradation signals may overlap protein-protein interaction surfaces, allowing a straightforward steric mechanism for regulated degradation. Analysis of alpha 2 degradation led to the identification of both 20S and 26S proteasome subunits, and several key features of proteasome assembly and active-site formation were subsequently uncovered. Finally, it has become clear that protein (poly)ubiquitination is highly dynamic in vivo, and our studies of yeast de-ubiquitinating enzymes illustrate how such enzymes can facilitate the proteolysis of diverse substrates.