Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast
Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast
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DOI：
10.1091/mbc.12.5.1303
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发表时间：
2001-05-01
影响因子：
3.3
通讯作者：
Brodsky, JL
中科院分区：
文献类型：
--
作者：
Zhang, YM;Nijbroek, G;Brodsky, JL
膜和分泌蛋白在内质网（ER）中折叠，错误折叠的蛋白可能被保留并靶向ER相关蛋白降解（ERAD）。为了阐明内质网中的膜蛋白降解的机制，我们研究了酵母酿酒酵母中囊性纤维化跨膜传导调节因子（CFTR）的命运。我们的数据表明，CFTR驻留在ER中，并在蛋白酶体活性缺陷或缺失泛素结合酶Ubc6p和Ubc7p的菌株中稳定，从而证明CFTR是酵母中真正的ERAD底物。我们还发现，热休克蛋白70（Hsp70），虽然不需要降解可溶性内腔ERAD基板，需要促进CFTR营业额。相反，钙连接蛋白和结合蛋白（BiP），这是所需的ER内腔蛋白在酵母和哺乳动物的蛋白水解，是固定的CFTR的降解，表明独特的机制，至少有一些可溶性和完整的膜ERAD基板在酵母中的处置。
Membrane and secretory proteins fold in the endoplasmic reticulum (ER), and misfolded proteins may be retained and targeted for ER-associated protein degradation (ERAD). To elucidate the mechanism by which an integral membrane protein in the ER is degraded, we studied the fate of the cystic fibrosis transmembrane conductance regulator (CFTR) in the yeast Saccharomyces cerevisiae. Our data indicate that CFTR resides in the ER and is stabilized in strains defective for proteasome activity or deleted for the ubiquitin-conjugating enzymes Ubc6p and Ubc7p, thus demonstrating that CFTR is a bona fide ERAD substrate in yeast. We also found that heat shock protein 70 (Hsp70), although not required for the degradation of soluble lumenal ERAD substrates, is required to facilitate CFTR turnover. Conversely, calnexin and binding protein (BiP), which are required for the proteolysis of ER lumenal proteins in both yeast and mammals, are dispensable for the degradation of CFTR, suggesting unique mechanisms for the disposal of at least some soluble and integral membrane ERAD substrates in yeast.