Feldman M, van der Goot F Gisou
Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH 1015 Lausanne, Switzerland.
Trends Cell Biol. 2009 Aug;19(8):357-63. doi: 10.1016/j.tcb.2009.05.005. Epub 2009 Jul 23.
Proteins of the endomembrane system undergo assisted folding in the endoplasmic reticulum (ER), then quality-control and, if misfolded, ER-associated degradation (ERAD). Recent findings on the biogenesis of a type-I membrane protein (an LRP6 mutant) lead us to hypothesize the existence of a novel mechanism promoting folding of membrane proteins from the cytosolic side of the ER. The proposed folding mechanism involves cycles of chaperone binding through mono-ubiquitylation and de-ubiquitylation, followed eventually by poly-ubiquitylation and ERAD. This suggests a novel dual role for ubiquitylation in the ER - dependent on the type of ubiquitin chains involved - in folding and in degradation, and highlights the potential importance of de-ubiquitylating enzymes.
内膜系统的蛋白质在内质网（ER）中进行辅助折叠，然后进行质量控制，若发生错误折叠，则进行内质网相关降解（ERAD）。最近关于一种I型膜蛋白（一种LRP6突变体）生物合成的研究结果使我们推测，存在一种从内质网胞质侧促进膜蛋白折叠的新机制。提出的折叠机制涉及通过单泛素化和去泛素化进行伴侣蛋白结合的循环，最终导致多泛素化和ERAD。这表明泛素化在内质网中具有一种新的双重作用——取决于所涉及的泛素链类型——在折叠和降解过程中发挥作用，并突出了去泛素化酶的潜在重要性。
