Broemer Meike, Meier Pascal
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK.
Trends Cell Biol. 2009 Mar;19(3):130-40. doi: 10.1016/j.tcb.2009.01.004. Epub 2009 Feb 13.
Ubiquitin is a protein modifier that is conjugated to target proteins either as a single moiety or as polyubiquitin chains. Over the past several years, an increasing number of ubiquitin ligases and ubiquitin-deconjugating enzymes have been identified; these modulate cell survival by degradative and non-degradative means. Mutations that affect ubiquitin-mediated signalling are tightly linked to various human pathologies including tumorigenesis. Unravelling how the ubiquitin-signal is conjugated, edited and 'read' is crucial to understanding cellular processes such as endocytic trafficking, NF-kappaB signalling, gene expression, DNA repair and apoptosis. In this review, we summarize recent advances that start to elucidate how the ubiquitin message is used as a versatile tool to regulate apoptosis, for example in the conjugation of ubiquitin to caspases. This results in steric interference with substrate entry and allosteric conformational impairment of the catalytic pocket of the caspase.
泛素是一种蛋白质修饰剂，它作为单个部分或多聚泛素链与靶蛋白结合。在过去几年中，越来越多的泛素连接酶和去泛素化酶被鉴定出来；它们通过降解和非降解方式调节细胞存活。影响泛素介导信号传导的突变与包括肿瘤发生在内的各种人类疾病紧密相关。阐明泛素信号是如何结合、编辑和“读取”的，对于理解诸如内吞运输、核因子κB信号传导、基因表达、DNA修复和细胞凋亡等细胞过程至关重要。在本综述中，我们总结了最近的进展，这些进展开始阐明泛素信息如何作为一种通用工具来调节细胞凋亡，例如泛素与半胱天冬酶的结合。这会导致空间位阻干扰底物进入以及半胱天冬酶催化口袋的变构构象受损。
