| First Author | Hagiwara M | Year | 2016 |
| Journal | Mol Cell | Volume | 63 |
| Issue | 5 | Pages | 753-67 |
| PubMed ID | 27570074 | Mgi Jnum | J:252992 |
| Mgi Id | MGI:6093944 | Doi | 10.1016/j.molcel.2016.07.014 |
| Citation | Hagiwara M, et al. (2016) Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e. Mol Cell 63(5):753-67 |
| abstractText | ER-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated posttranscriptionally and independently of the unfolded protein response by adjusting the endogenous levels of EDEM1, OS-9, and SEL1L (ERAD enhancers). Functional UBC6e requires its precise location in the ER to form a supramolecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e's enzymatic activity. Ablation of UBC6e causes upregulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowly in vitro and in vivo. The levels of proteins that comprise the ERAD machinery are thus carefully tuned and adjusted to prevailing needs. |
