蛋白酶体依赖性内质网相关蛋白降解：通往熟悉命运的非常规途径。
Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate.
作者信息
Werner E D, Brodsky J L, McCracken A A
机构信息
Biology Department, University of Nevada, Reno 89557, USA.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13797-801. doi: 10.1073/pnas.93.24.13797.
Abstract
Until recently, the degradation of aberrant and unassembled proteins retained in the endoplasmic reticulum (ER) was thought to involve unidentified ER-localized proteases. We now show that the ER-associated degradation (ERAD) of two mutant proteins that accumulate in the ER lumen is inhibited in a proteasome-defective yeast strain and when cytosol from this mutant is used in an in vitro assay. In addition, ERAD is limited in vitro in the presence of the proteasome inhibitors, 3,4-dichloroisocoumarin and lactacystin. Furthermore, we find that an ERAD substrate is exported from ER-derived microsomes, and the accumulation of exported substrate is 2-fold greater when proteasome mutant cytosol is used in place of wild-type cytosol. We conclude that lumenal ERAD substrates are exported from the yeast ER to the cytoplasm for degradation by the proteasome complex.
摘要
直到最近，人们还认为，保留在内质网（ER）中的异常和未组装蛋白质的降解涉及尚未确定的内质网定位蛋白酶。我们现在表明，在内质网腔中积累的两种突变蛋白的内质网相关降解（ERAD）在蛋白酶体缺陷的酵母菌株中受到抑制，并且当使用该突变体的胞质溶胶进行体外测定时也受到抑制。此外，在蛋白酶体抑制剂3,4-二氯异香豆素和乳胞素存在的情况下，ERAD在体外受到限制。此外，我们发现一种ERAD底物从内质网衍生的微粒体中输出，当使用蛋白酶体突变体胞质溶胶代替野生型胞质溶胶时，输出底物的积累增加了2倍。我们得出结论，内质网腔ERAD底物从酵母内质网输出到细胞质中，由蛋白酶体复合物进行降解。
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