Degradation-mediated protein quality control in the nucleus
Degradation-mediated protein quality control in the nucleus
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DOI：
10.1016/j.cell.2005.01.016
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发表时间：
2005-03-25
期刊：
影响因子：
64.5
通讯作者：
Gottschling, DE
中科院分区：
文献类型：
--
作者：
Gardner, RG;Nelson, ZW;Gottschling, DE
蛋白质质量控制降解系统消除细胞中的异常蛋白质，防止对正常细胞功能产生有害影响。尽管此类系统已在大多数亚细胞区室中被发现，但在细胞核中尚未发现。在这里，我们报告了在酿酒酵母中发现的这样一个系统。它由 San1p 定义，San1p 是一种泛素蛋白连接酶，与泛素结合酶 Cdc34p 和 Ubc1p 结合，靶向四种不同的突变核蛋白，从而被蛋白酶体泛素化和破坏。 San1p 对异常蛋白质具有精确的特异性，并且不针对其突变底物的野生型版本。 San1p 是核定位的，需要核定位才能发挥功能。 SAN1 的缺失会导致慢性应激反应，强调了其在细胞中蛋白质质量控制的作用。我们认为 San1p 介导的降解是蛋白水解防御的最后一道防线，防止细胞核中异常蛋白质的有害积累，并且其他真核生物中也存在类似的系统。
Protein quality control degradation systems rid the cell of aberrant proteins, preventing detrimental effects on normal cellular function. Although such systems have been identified in most subcellular compartments, none have been found in the nucleus. Here, we report the discovery of such a system in Saccharomyces cerevisiae. It is defined by San1p, a ubiquitin-protein ligase that, in conjunction with the ubiquitin-conjugating enzymes Cdc34p and Ubc1p, targets four distinct mutant nuclear proteins for ubiquitination and destruction by the proteasome. San1p has exquisite specificity for aberrant proteins and does not target the wild-type versions of its mutant substrates. San1p is nuclear localized and requires nuclear localization for function. Loss of SAN1 results in a chronic stress response, underscoring its role of protein quality control in the cell. We propose that San1p-mediated degradation acts as the last line of proteolytic defense against the deleterious accumulation of aberrant proteins in the nucleus and that analogous systems exist in other eukaryotes.