20S proteasomes and protein degradation "by default"
20S proteasomes and protein degradation "by default"
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DOI：
10.1002/bies.20447
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发表时间：
2006-08-01
期刊：
影响因子：
4
通讯作者：
Shaul, Yosef
中科院分区：
文献类型：
--
作者：
Asher, Gad;Reuven, Nina;Shaul, Yosef
大多数细胞蛋白质的降解是由蛋白酶体介导的。泛素依赖的蛋白酶体蛋白降解是由许多酶执行的，这些酶在底物与26S蛋白酶体结合之前相互作用来修饰底物。或者，某些蛋白质天生不稳定，会被20S蛋白酶体“默认”降解。令人费解的是，蛋白质大体上受到这两种降解途径的影响。具有非结构区域的蛋白质在体外被发现是20S蛋白酶体的底物，因此，非结构区域可能在细胞中作为蛋白质降解的信号。文献中充斥着这样的例子，即蛋白质结合到更大的复合体中可以增加蛋白质的稳定性，可能是通过“默认”逃脱降解。我们的模型认为，蛋白质复合体的形成掩盖了非结构化区域，使它们无法进入20s蛋白酶体。该模型不仅为最近提出的“合作稳定性”理论提供了分子解释，而且在蛋白质调节和功能领域引发了新的预测和解释。
The degradation of the majority of cellular proteins is mediated by the proteasomes. Ubiquitin-dependent proteasomal protein degradation is executed by a number of enzymes that interact to modify the substrates prior to their engagement with the 26S proteasomes. Alternatively, certain proteins are inherently unstable and undergo "default" degradation by the 20S proteasomes. Puzzlingly, proteins are by large subjected to both degradation pathways. Proteins with unstructured regions have been found to be substrates of the 20S proteasomes in vitro and, therefore, unstructured regions may serve as signals for protein degradation "by default" in the cell. The literature is loaded with examples where engagement of a protein into larger complexes increases protein stability, possibly by escaping degradation "by default". Our model suggests that formation of protein complexes masks the unstructured regions, making them inaccessible to the 20S proteasomes. This model not only provides molecular explanations for a recent theoretical "cooperative stability" principle, but also provokes new predictions and explanations in the field of protein regulation and functionality.