文章：

IAPs：从半胱天冬酶抑制剂到NF-κB、炎症和癌症调节剂

IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer

原文发布日期：2010-08-01

DOI: 10.1038/nrc2889

类型: Review Article

开放获取: 否

要点：

1. Alterations in inhibitor of apoptosis (IAP) proteins are prevalent in many types of human cancer and are associated with chemoresistance, disease progression and poor prognosis.
2. IAPs are best known for their ability to regulate caspases; however, IAPs also influence a multitude of other cellular processes.
3. Possibly the most important contribution of IAPs to cell survival and tumorigenesis resides in the ability of cIAP1, cIAP2 and XIAP to regulate ubiquitin-dependent activation of nuclear factor-κB (NF-κB) and innate immune responses.
4. Constitutive activation of NF-κB and chronic inflammation both have a major role in tumour development and are seen in most tumour types, including leukaemia, lymphomas and solid tumours.
5. NF-κB can be activated through the canonical and non-canonical signal transduction cascade, and cIAPs are crucial regulators of both these pathways.
6. cIAPs are also indispensable in protecting cancer cells from the lethal effects of tumour necrosis factor receptor 1 activation.
7. Small-molecule IAP antagonists, termed Smac mimetics, cause the rapid depletion of cIAPs and show potent anti-tumorigenic activity in vitro and in vivo.

要点翻译：

1. 细胞凋亡抑制蛋白（IAP）的改变在多种人类癌症中普遍存在，并与化疗耐药、疾病进展和不良预后相关。
2. IAPs最为人熟知的功能是调控半胱天冬酶，然而它们还影响众多其他细胞过程。
3. IAPs对细胞存活和肿瘤发生最重要的贡献可能在于cIAP1、cIAP2和XIAP能够调节核因子κB（NF-κB）的泛素依赖性激活及先天免疫应答。
4. NF-κB的组成性激活和慢性炎症在肿瘤发展中均起重要作用，可见于白血病、淋巴瘤和实体瘤等大多数肿瘤类型。
5. NF-κB可通过经典和非经典信号转导级联反应激活，而cIAPs是这两条通路的关键调节因子。
6. cIAPs在保护癌细胞免受肿瘤坏死因子受体1激活的致死效应中也不可或缺。
7. 小分子IAP拮抗剂（称为Smac模拟物）能导致cIAPs快速耗竭，并在体外和体内显示出强大的抗肿瘤活性。

英文摘要：

The realization that alterations in inhibitor of apoptosis (IAP) proteins are found in many types of human cancer and are associated with chemoresistance, disease progression and poor prognosis, has sparked a worldwide frenzy in the development of small pharmacological inhibitors of IAPs. The development of such inhibitors has radically changed our knowledge of the signalling processes that are regulated by IAPs. Recent studies indicate that IAPs not only regulate caspases and apoptosis, but also modulate inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis.

摘要翻译： 

人们发现，凋亡抑制蛋白（IAP）的异常在多种人类肿瘤中普遍存在，并且与化疗耐药、疾病进展及不良预后密切相关，这一认识在全球范围内掀起了研发IAP小分子抑制剂的热潮。此类抑制剂的开发彻底改变了我们对IAP所调控信号通路的理解。最新研究表明，IAP不仅调控caspase和细胞凋亡，还参与调节炎症信号与免疫、促分裂原激酶信号、细胞增殖与有丝分裂，以及细胞侵袭和转移。

原文链接：

IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer