The extent of Ssa1/Ssa2 Hsp70 chaperone involvement in nuclear protein quality control degradation varies with the substrate
The extent of Ssa1/Ssa2 Hsp70 chaperone involvement in nuclear protein quality control degradation varies with the substrate
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DOI：
10.1091/mbc.e18-02-0121
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发表时间：
2020-02-01
影响因子：
3.3
通讯作者：
Gardner, Richard G.
中科院分区：
文献类型：
--
作者：
Jones, Ramon D.;Enam, Charisma;Gardner, Richard G.
蛋白质错误折叠是细胞必须管理的一种反复出现的现象;否则，错误折叠的蛋白质如果持续存在，就会聚集并变得有毒。为了应对这一负担，细胞已经进化出蛋白质质量控制（PQC）机制，以管理错误折叠的蛋白质。在PQC中起作用的两类系统是帮助蛋白质折叠的分子伴侣和泛素-蛋白质连接酶，所述泛素-蛋白质连接酶将错误折叠的蛋白质泛素化以用于蛋白酶体降解。折叠和降解PQC系统如何相互作用和协调各自的功能尚未完全了解。以往对内质网和胞质溶胶中PQC降解途径的研究已导致普遍认为这些途径需要Hsp 70分子伴侣的活性。在这里，我们发现，参与芽殖酵母Hsp 70分子伴侣Ssa 1和Ssa 2在核PQC降解与基板的变化。特别是，由酵母泛素蛋白连接酶San 1介导的核PQC降解通常涉及Ssa 1/Ssa 2，但San 1底物识别和泛素化可以在体内和体外没有这些Hsp 70分子伴侣功能的情况下进行。我们的研究提供了新的见解的变化Hsp 70分子伴侣参与核PQC降解途径。
Protein misfolding is a recurring phenomenon that cells must manage; otherwise misfolded proteins can aggregate and become toxic should they persist. To counter this burden, cells have evolved protein quality control (PQC) mechanisms that manage misfolded proteins. Two classes of systems that function in PQC are chaperones that aid in protein folding and ubiquitin-protein ligases that ubiquitinate misfolded proteins for proteasomal degradation. How folding and degradative PQC systems interact and coordinate their respective functions is not yet fully understood. Previous studies of PQC degradation pathways in the endoplasmic reticulum and cytosol have led to the prevailing idea that these pathways require the activity of Hsp70 chaperones. Here, we find that involvement of the budding yeast Hsp70 chaperones Ssa1 and Ssa2 in nuclear PQC degradation varies with the substrate. In particular, nuclear PQC degradation mediated by the yeast ubiquitin-protein ligase San1 often involves Ssa1/Ssa2, but San1 substrate recognition and ubiquitination can proceed without these Hsp70 chaperone functions in vivo and in vitro. Our studies provide new insights into the variability of Hsp70 chaperone involvement with a nuclear PQC degradation pathway.