From trash collectors to guardians of cell signaling and immune homeostasis.
From trash collectors to guardians of cell signaling and immune homeostasis.
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从垃圾收集器到细胞信号和免疫稳态的监护人。
DOI：
10.1111/imr.12317
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发表时间：
2015-07
影响因子：
8.7
通讯作者：
Ma A
中科院分区：
文献类型：
--
作者：
Ma A
泛素化是泛素分子与目标蛋白质的共价结合，发生迅速且经常是可逆的，并调节作为细胞免疫反应基础的大量蛋白质-蛋白质相互作用[1]。泛素化最为人所知的是调节蛋白质与降解蛋白酶体的相互作用，从而决定蛋白质的稳定性。这一关键功能得到了2004年诺贝尔化学奖的认可。最近的研究表明，泛素化还介导了调节蛋白质运输、转录因子复合体和信号转导的蛋白质之间广泛的非蛋白质水解性相互作用[2]。在这一卷中，综述文章使用了单个泛素连接酶的镜头来调节免疫细胞中信号蛋白的泛素化。尽管其他翻译后修饰通常以二元方式改变蛋白质(例如，磷酸化和非磷酸化)，泛素化发生在多种生化构象中，从而提供了对蛋白质命运的更大规格。泛素化是指泛素分子链通过七种赖氨酸之一或泛素上的N端蛋氨酸连接在一起。所有八种构象的泛素链都存在于细胞中，也描述了单个泛素分子与靶蛋白的结合。重要的是，泛素化的生物化学复杂性给修饰的靶标赋予了不同的生物学后果。不同类型的多泛素链被不同的泛素结合蛋白或泛素传感器识别。例如，蛋白质与K48连接的泛素链的结合招募降解的蛋白酶体，而与K63连接的或M1连接的链结合的蛋白质通常招募具有结合这些链的能力的其他信号蛋白(3，4)(图1)。
Ubiquitination, the covalent attachment of ubiquitin molecules to target proteins, occurs rapidly and often reversibly, and regulates a vast array of protein-protein interactions that underlie cellular immune responses (1). Ubiquitination is best known for mediating protein interactions with degradative proteasomes, thereby dictating protein stability. This critical function was recognized by the Nobel Prize in Chemistry in 2004. Recent studies indicate that ubiquitination also mediates a broad array of non-proteolytic interactions between proteins that regulate protein trafficking, transcription factor complexes, and signal transduction (2). In this volume, the review articles utilize the lens of individual ubiquitin ligase enzymes that regulate ubiquitination of signaling proteins in immune cells.While other post-translational modifications typically alter proteins in a binary fashion (eg phosphorylated vs. non-phosphorylated), ubiquitination occurs in multiple biochemical conformations, thereby affording greater specification of protein fate. Ubiquitination involves chains of ubiquitin molecules linked via one of the seven lysines or the N-terminal methionine on ubiquitin. All eight conformations of ubiquitin chains exist in cells, and attachment of single ubiquitin molecules to target proteins has also been described. Importantly, the biochemical complexity of ubiquitination confers diverse biological consequences upon modified targets. Distinct types of polyubiquitin chains are recognized by different ubiquitin binding proteins, or ubiquitin sensors. For example, conjugation of proteins with K48-linked ubiquitin chains recruits degradative proteasomes, while proteins conjugated with K63-linked or M1-linked chains typically recruit other signaling proteins with the capacity to bind these chains (3, 4)(Fig. 1).
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