Tiwari S, Weissman A M
Laboratory of Immune Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-1152, USA.
J Biol Chem. 2001 May 11;276(19):16193-200. doi: 10.1074/jbc.M007640200. Epub 2001 Feb 2.
Degradation of proteins from the endoplasmic reticulum is fundamental to quality control within the secretory pathway, serves as a way of regulating levels of crucial proteins, and is utilized by viruses to enhance pathogenesis. In yeast two ubiquitin-conjugating enzymes (E2s), UBC6p and UBC7p are implicated in this process. We now report the characterization of murine homologs of these E2s. MmUBC6 is an integral membrane protein that is anchored via its hydrophobic C-terminal tail to the endoplasmic reticulum. MmUBC7, which is not an integral membrane protein, shows significant endoplasmic reticulum colocalization with MmUBC6. Overexpression of catalytically inactive MmUBC7 significantly delayed degradation from the endoplasmic reticulum of two T cell antigen receptor subunits, alpha and CD3-delta, and suggests a role for the ubiquitin conjugating system at the initiation of retrograde movement from the endoplasmic reticulum. These findings also implicate, for the first time, a specific E2 in degradation from the endoplasmic reticulum in mammalian cells.
内质网蛋白质的降解对于分泌途径中的质量控制至关重要，是调节关键蛋白质水平的一种方式，并且被病毒用于增强致病性。在酵母中，两种泛素结合酶（E2s），UBC6p和UBC7p参与了这一过程。我们现在报告这些E2s的小鼠同源物的特征。MmUBC6是一种整合膜蛋白，通过其疏水的C末端尾巴锚定在内质网上。MmUBC7不是整合膜蛋白，与MmUBC6在内质网中有显著的共定位。催化失活的MmUBC7的过表达显著延迟了两种T细胞抗原受体亚基α和CD3-δ从内质网的降解，并表明泛素结合系统在内质网逆行运动起始时发挥作用。这些发现还首次表明了一种特定的E2在哺乳动物细胞内质网降解中的作用。
