Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0310 Oslo, Norway.
J Cell Sci. 2012 Jan 15;125(Pt 2):265-75. doi: 10.1242/jcs.091280.
Ligand-induced activation of transmembrane receptors activates intracellular signaling cascades that control vital cellular processes, such as cell proliferation, differentiation, migration and survival. Receptor signaling is modulated by several mechanisms to ensure that the correct biological outcome is achieved. One such mechanism, which negatively regulates receptor signaling, involves the modification of receptors with ubiquitin. This post-translational modification can promote receptor endocytosis and targets receptors for lysosomal degradation, thereby ensuring termination of receptor signaling. In this Commentary, we review the roles of ubiquitylation in receptor endocytosis and degradative endosomal sorting by drawing on the epidermal growth factor receptor (EGFR) as a well-studied example. Furthermore, we elaborate on the molecular basis of ubiquitin recognition along the endocytic pathway through compartment-specific ubiquitin-binding proteins and highlight how endocytic sorting machineries control these processes. In addition, we discuss the importance of ubiquitin-dependent receptor endocytosis for the maintenance of cellular homeostasis and in the prevention of diseases such as cancer.
配体诱导跨膜受体的激活会激活细胞内信号级联反应，从而控制细胞增殖、分化、迁移和存活等重要的细胞过程。受体信号受多种机制调节，以确保实现正确的生物学结果。其中一种负调节受体信号的机制涉及用泛素修饰受体。这种翻译后修饰可以促进受体内化，并将受体靶向溶酶体降解，从而确保受体信号的终止。在这篇评论中，我们以研究较为充分的表皮生长因子受体 (EGFR) 为例，综述了泛素化在受体内化和降解性内体分拣中的作用。此外，我们详细阐述了沿内吞途径的泛素识别的分子基础，以及内吞分拣机制如何控制这些过程。此外，我们还讨论了泛素依赖性受体内化对于维持细胞内稳态以及预防癌症等疾病的重要性。
