文章：

A20：从泛素编辑到肿瘤抑制

A20: from ubiquitin editing to tumour suppression

原文发布日期：2010-04-12

DOI: 10.1038/nrc2775

类型: Review Article

开放获取: 否

要点：

1. Protracted activation of the immune system by persistent inflammation or chronic infection can be oncogenic.
2. Nuclear factor-κB (NF-κB) transcription factors are normally activated in a transient manner in response to inflammation, infection and other cellular stresses to provide pro-inflammatory and pro-survival signals to regain homeostasis.
3. Failure to downregulate persistent NF-κB signalling can instead facilitate the manifestation of all six hallmarks of cancer: self-sufficient cell growth, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.
4. Ubiquitylation is a post-translational modification that tightly regulates the activity of signalling proteins in NF-κB transduction cascades.
5. A20 is a central regulator of inflammation and functions as a ubiquitin-editing enzyme to potently downregulate NF-κB signalling.
6. A20 is inactivated in various haematological malignancies and results in constitutive NF-κB activation in tumour cells; therefore, A20 is a crucial tumour suppressor.
7. The identification of A20 as a tumour suppressor establishes new links between ubiquitylation, NF-κB activation and tumorigenesis that may be exploited in the clinic for improved patient care.

要点翻译：

1. 免疫系统因持续炎症或慢性感染而长期激活可能具有致癌性。
2. 核因子-κB（NF-κB）转录因子通常在应对炎症、感染及其他细胞应激时以瞬时方式激活，通过提供促炎和促生存信号以恢复稳态。
3. 若未能下调持续的NF-κB信号传导，则会促进癌症六大标志的表现：细胞自主生长、对生长抑制信号不敏感、凋亡逃逸、无限复制潜能、持续血管生成以及组织浸润与转移。
4. 泛素化是一种翻译后修饰，可精确调控NF-κB信号转导级联中信号蛋白的活性。
5. A20是炎症的核心调控因子，作为泛素编辑酶有效下调NF-κB信号传导。
6. 该蛋白在多种血液系统恶性肿瘤中失活，导致肿瘤细胞中NF-κB持续性激活，因此A20是至关重要的肿瘤抑制因子。
7. A20肿瘤抑制功能的确认建立了泛素化、NF-κB激活与肿瘤发生之间的新联系，这一发现有望在临床中应用于改善患者诊疗。

英文摘要：

Clinicians have suspected for hundreds of years that chronic activation of the immune system contributes to the development of cancer. However, the molecular mechanisms that mediate this precarious interplay are only now being elucidated. Recent reports have identified A20 as a crucial tumour suppressor in various lymphomas. A20 is a ubiquitin-editing enzyme that attenuates the activity of proximal signalling complexes at pro-inflammatory receptors. In this Review we summarize the evidence linking chronic inflammation with tumorigenesis and consider how A20 modulates inflammatory signalling cascades, thereby providing a mechanism to explain how deregulation of ubiquitylation can promote tumorigenesis.

摘要翻译： 

临床医生数百年来一直推测，免疫系统的慢性激活会促进癌症的发生。然而，介导这种危险相互作用的分子机制直到最近才被阐明。最新研究确认，A20 是多种淋巴瘤中至关重要的肿瘤抑制因子。A20 是一种泛素编辑酶，能够削弱促炎受体近端信号复合物的活性。在本综述中，我们总结了慢性炎症与肿瘤发生相关联的证据，并探讨 A20 如何调控炎症信号级联反应，从而阐明泛素化失调如何促进肿瘤发生的机制。

原文链接：

A20: from ubiquitin editing to tumour suppression