Mayer T U, Braun T, Jentsch S
ZMBH, Zentrum für Molekulare Biologie er Universität Heidelberg, Heidelberg, Germany.
EMBO J. 1998 Jun 15;17(12):3251-7. doi: 10.1093/emboj/17.12.3251.
Selective degradation of proteins at the endoplasmic reticulum (ER-associated degradation) is thought to proceed largely via the cytosolic ubiquitin-proteasome pathway. Recent data have indicated that the dislocation of short-lived integral-membrane proteins to the cytosolic proteolytic system may require components of the Sec61 translocon. Here we show that the proteasome itself can participate in the extraction of an ER-membrane protein from the lipid bilayer. In yeast mutants expressing functionally attenuated proteasomes, degradation of a short-lived doubly membrane-spanning protein proceeds rapidly through the N-terminal cytosolic domain of the substrate, but slows down considerably when continued degradation of the molecule requires membrane extraction. Thus, proteasomes engaged in ER degradation can directly process transmembrane proteins through a mechanism in which the dislocation of the substrate and its proteolysis are coupled. We therefore propose that the retrograde transport of short-lived substrates may be driven through the activity of the proteasome.
内质网处蛋白质的选择性降解（内质网相关降解）被认为主要通过胞质泛素 - 蛋白酶体途径进行。最近的数据表明，短命整合膜蛋白向内质网的移位可能需要Sec61转运体的成分。在这里，我们表明蛋白酶体本身可以参与从脂质双层中提取内质网膜蛋白。在表达功能减弱的蛋白酶体的酵母突变体中，一种短命的双跨膜蛋白的降解通过底物的N端胞质结构域迅速进行，但当分子的持续降解需要膜提取时，降解速度会大大减慢。因此，参与内质网降解的蛋白酶体可以通过一种将底物移位与其蛋白水解偶联的机制直接处理跨膜蛋白。我们因此提出，短命底物的逆行转运可能是由蛋白酶体的活性驱动的。
