Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
EMBO J. 2022 Mar 15;41(6):e109845. doi: 10.15252/embj.2021109845. Epub 2022 Feb 16.
The endoplasmic reticulum (ER) is a large, dynamic, and multifunctional organelle. ER protein homeostasis is essential for the coordination of its diverse functions and depends on ER-associated protein degradation (ERAD). The latter process selects target proteins in the lumen and membrane of the ER, promotes their ubiquitination, and facilitates their delivery into the cytosol for degradation by the proteasome. Originally characterized for a role in the degradation of misfolded proteins and rate-limiting enzymes of sterol biosynthesis, the many branches of ERAD now appear to control the levels of a wider range of substrates and influence more broadly the organization and functions of the ER, as well as its interactions with adjacent organelles. Here, we discuss recent mechanistic advances in our understanding of ERAD and of its consequences for the regulation of ER functions.
内质网（ER）是一个大型的、动态的和多功能的细胞器。内质网蛋白的稳态对于协调其多种功能是必不可少的，并且依赖于内质网相关蛋白降解（ERAD）。后一过程选择内质网腔和膜中的靶蛋白，促进它们的泛素化，并有助于它们被递送到细胞质中，由蛋白酶体降解。最初的特征是在降解错误折叠的蛋白质和固醇生物合成的限速酶中起作用，现在 ERAD 的许多分支似乎控制着更广泛的底物水平，并更广泛地影响 ER 的组织和功能，以及它与相邻细胞器的相互作用。在这里，我们讨论了我们对内质网相关蛋白降解及其对内质网功能调节的影响的理解的最新机制进展。
