Unité Propre de Recherche 2357, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire des Plantes, Conventionné avec l'Université de Strasbourg, Strasbourg, France.
EMBO J. 2013 Aug 28;32(17):2307-20. doi: 10.1038/emboj.2013.173. Epub 2013 Aug 2.
Protein ubiquitylation is a post-translational modification that controls all aspects of eukaryotic cell functionality, and its defective regulation is manifested in various human diseases. The ubiquitylation process requires a set of enzymes, of which the ubiquitin ligases (E3s) are the substrate recognition components. Modular CULLIN-RING ubiquitin ligases (CRLs) are the most prevalent class of E3s, comprising hundreds of distinct CRL complexes with the potential to recruit as many and even more protein substrates. Best understood at both structural and functional levels are CRL1 or SCF (SKP1/CUL1/F-box protein) complexes, representing the founding member of this class of multimeric E3s. Another CRL subfamily, called CRL3, is composed of the molecular scaffold CULLIN3 and the RING protein RBX1, in combination with one of numerous BTB domain proteins acting as substrate adaptors. Recent work has firmly established CRL3s as major regulators of different cellular and developmental processes as well as stress responses in both metazoans and higher plants. In humans, functional alterations of CRL3s have been associated with various pathologies, including metabolic disorders, muscle, and nerve degeneration, as well as cancer. In this review, we summarize recent discoveries on the function of CRL3s in both metazoans and plants, and discuss their mode of regulation and specificities.
蛋白质泛素化是一种翻译后修饰，控制真核细胞功能的各个方面，其调节缺陷表现在各种人类疾病中。泛素化过程需要一组酶，其中泛素连接酶 (E3s) 是底物识别成分。模块化 CULLIN-RING 泛素连接酶 (CRLs) 是最常见的 E3 类，包含数百种不同的 CRL 复合物，具有招募尽可能多甚至更多蛋白质底物的潜力。在结构和功能水平上理解得最好的是 CRL1 或 SCF（SKP1/CUL1/F-box 蛋白）复合物，它代表了这种多聚 E3 类的创始成员。另一个 CRL 亚家族，称为 CRL3，由分子支架 CULLIN3 和 RING 蛋白 RBX1 组成，与众多作为底物接头的 BTB 结构域蛋白之一结合。最近的工作已将 CRL3 确定为真核生物和高等植物中不同细胞和发育过程以及应激反应的主要调节剂。在人类中，CRL3 的功能改变与各种病理学有关，包括代谢紊乱、肌肉和神经退化以及癌症。在这篇综述中，我们总结了最近在真核生物和植物中 CRL3 功能的发现，并讨论了它们的调节方式和特异性。
