The transcription factor nuclear factor-kappa B and cancer
The transcription factor nuclear factor-kappa B and cancer
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DOI：
10.1016/j.clon.2006.11.013
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Zamora, A.
中科院分区：
文献类型：
--
作者：
Escarcega, R. O.;Fuentes-Alexandro, S.;Zamora, A.
自从1986年发现核因子-κ B（NF-κ B）以来，已经进行了许多研究，显示NF-κ B信号通路和炎症反应的控制之间的联系。如今，众所周知，炎症反应和细胞凋亡的控制与NF-κ B的活化密切相关。存在三种NF-κ B活化途径。第一种（经典途径）通常在微生物和病毒感染或暴露于激活三重IKK复合物的促炎细胞因子时触发，导致磷酸化诱导的I κ B降解，主要依赖于IKK β活性。第二种途径（替代途径），通过诱导NF-κ B2/p100前体蛋白的加工，导致p52：RelB二聚体的选择性活化，其主要在细胞质中与RelB形成异源二聚体。该途径由肿瘤坏死因子细胞因子家族的某些成员通过上游激酶NIK选择性激活IKK α同型二聚体而触发。第三条途径称为CK 2，不依赖IKK。NF-κ B通过转录抗凋亡蛋白发挥作用，导致细胞增殖和肿瘤生长增加。还已知一些药物直接作用于NF-κ B的抑制，从而产生细胞凋亡的调节;一些实例是阿司匹林和皮质类固醇。本文综述了NF-κ B在细胞凋亡调控中的作用、与肿瘤发生的关系、NF-κ B活化与多种肿瘤的关系以及NF-κ B作为肿瘤治疗靶点的研究进展。
Since the discovery of nuclear factor-kappa B (NF-kappa B) in 1986, many studies have been conducted showing the link between the NF-kappa B signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF-kappa B. Three NF-kappa B activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphoryiation-induced I kappa B degradation and depends mainly on IKK beta activity. The second (the alternative pathway), leads to selective activation of p52:RelB dimers by inducing the processing of the NF-kappa B2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKK alpha homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-kappa B acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-kappa B, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-kappa B in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-kappa B activation is closely related to different cancers, and finally the potential target of NF-kappa B as cancer therapy.