非经典 NF-κB 信号通路。
Non-canonical NF-κB signaling pathway.
机构信息
Department of Immunology, The University of Texas MD Anderson Cancer Center, The University of Texas Graduate School of Biomedical Sciences at Houston, 7455 Fannin Street, Box 902, Houston, TX 77030, USA.
出版信息
Cell Res. 2011 Jan;21(1):71-85. doi: 10.1038/cr.2010.177. Epub 2010 Dec 21.
Abstract
The non-canonical NF-κB pathway is an important arm of NF-κB signaling that predominantly targets activation of the p52/RelB NF-κB complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A central signaling component of the non-canonical pathway is NF-κB-inducing kinase (NIK), which integrates signals from a subset of TNF receptor family members and activates a downstream kinase, IκB kinase-α (IKKα), for triggering p100 phosphorylation and processing. A unique mechanism of NIK regulation is through its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction complex and signal-induced non-canonical NF-κB signaling involves NIK stabilization. Tight control of the fate of NIK is important, since deregulated NIK accumulation is associated with lymphoid malignancies.
摘要
非经典 NF-κB 通路是 NF-κB 信号转导的一个重要分支，主要靶向 p52/RelB NF-κB 复合物的激活。该通路依赖于 p100 的诱导加工，p100 分子既是 p52 的前体，也是 RelB 特异性抑制剂。非经典通路的一个核心信号成分是 NF-κB 诱导激酶 (NIK)，它整合了 TNF 受体家族成员的一部分信号，并激活下游激酶 IκB 激酶-α (IKKα)，以触发 p100 磷酸化和加工。NIK 调节的一个独特机制是通过其命运控制：TRAF-cIAP 破坏复合物将 NIK 的基础水平保持在较低水平，信号诱导的非经典 NF-κB 信号转导涉及 NIK 稳定。NIK 命运的严格控制很重要，因为 NF-κB 信号转导涉及 NIK 稳定。NIK 积累失调与淋巴恶性肿瘤有关。
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