INVIVO DEGRADATION OF A TRANSCRIPTIONAL REGULATOR - THE YEAST ALPHA-2 REPRESSOR
INVIVO DEGRADATION OF A TRANSCRIPTIONAL REGULATOR - THE YEAST ALPHA-2 REPRESSOR
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DOI：
10.1016/0092-8674(90)90481-s
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发表时间：
1990-05-18
期刊：
影响因子：
64.5
通讯作者：
VARSHAVSKY, A
中科院分区：
文献类型：
--
作者：
HOCHSTRASSER, M;VARSHAVSKY, A
代谢不稳定性是调节蛋白的特征，其体内浓度必须随时间变化。酵母S.这里显示酿酒酵母的半衰期仅为约1/3。α 2的两个结构域中的每一个都携带一个序列，该序列可以独立地靶向正常长寿命的蛋白质以进行快速破坏。此外，这两个退化信号显示通过不同的机制进行操作。已分离出α 2降解缺陷的突变体，并发现其具有许多额外的缺陷，表明负责α 2周转的途径包括具有多种功能的组分。最后，我们证明了一个短寿命的寡聚蛋白质亚基可以在体内降解，而不破坏其他，长寿命的亚基相同的蛋白质。这种亚基特异性降解使得一种新型的翻译后重构成为可能，在这种重构中，异聚体蛋白可以通过选择性的、降解介导的亚基替换来进行功能修饰。
Metabolic instability is characteristic of regulatory proteins whose in vivo concentrations must vary as a function of time. The cell type-specific .alpha.2 repressor of the yeast S. cerevisiae is shown here to have a half-life of only .apprx. 5 min. Each of the two structural domains of .alpha.2 carries a sequence that can independent target a normally long-lived protein for rapid destruction. Moreover, these two degradation signals are shown to operate via distinct mechanisms. Mutants deficient in the degradation of .alpha.2 have been isolated and found to have a number of additional defects, indicating that the pathways responsible for .alpha.2 turnover include components with multiple functions. Finally, we demonstrate that a short-lived subunit of an oligomeric protein can be degraded in vivo without destabilizing other, long lived subunits of the same protein. This subunit-specific degradation makes possible a novel type of posttranslational remodeling in which a heteromeric protein could be functionallymodified by selective, degradation-mediated replacement of its subunits.