AMAP1 as a negative-feedback regulator of nuclear factor-κB under inflammatory conditions.
AMAP1 as a negative-feedback regulator of nuclear factor-κB under inflammatory conditions.
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DOI：
10.1038/srep05094
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发表时间：
2014-05-28
影响因子：
4.6
通讯作者：
Ashida N
中科院分区：
文献类型：
--
作者：
Tien DN;Kishihata M;Yoshikawa A;Hashimoto A;Sabe H;Nishi E;Kamei K;Arai H;Kita T;Kimura T;Yokode M;Ashida N
NF-κB是一种重要的转录因子，可调节包括炎症在内的多种细胞功能，因此，对其进行适当的调控具有重要意义。其激活的详细机制已被很好地表征，但负调控的机制知之甚少。在这项研究中，我们发现AMAP 1是一种Arf-GT酶激活蛋白，通过与NF-κB信号转导中的一种必需激酶IKKβ结合，作为NF-κB的负反馈调节剂。蛋白质组学分析证实AMAP 1是IKKβ的结合蛋白。AMAP 1过表达通过干扰IKKβ与NEMO的结合抑制NF-κB活性，而AMAP 1缺失则增强NF-κB活性。NF-κB的活化可诱导AMAP 1从细胞膜和细胞核转位至细胞质，从而增强AMAP 1与IKKβ的相互作用。这些结果证明了AMAP 1作为NF-κB负反馈调节剂的新作用，并将其作为抗炎治疗的可能靶点。
NF-κB is a major transcriptional factor regulating many cellular functions including inflammation; therefore, its appropriate control is of high importance. The detailed mechanism of its activation has been well characterized, but that of negative regulation is poorly understood. In this study, we showed AMAP1, an Arf-GTPase activating protein, as a negative feedback regulator for NF-κB by binding with IKKβ, an essential kinase in NF-κB signaling. Proteomics analysis identified AMAP1 as a binding protein with IKKβ. Overexpression of AMAP1 suppressed NF-κB activity by interfering the binding of IKKβ and NEMO, and deletion of AMAP1 augmented NF-κB activity. The activation of NF-κB induced translocation of AMAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of AMAP1 and IKKβ. These results demonstrated a novel role of AMAP1 as a negative feedback regulator of NF-κB, and presented it as a possible target for anti-inflammatory treatments.
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DOI：
10.1083/jcb.201201065
发表时间：
2012-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Onodera Y;Nam JM;Hashimoto A;Norman JC;Shirato H;Hashimoto S;Sabe H
通讯作者：
Sabe H
DOI：
10.1073/pnas.070552297
发表时间：
2000-04-11
影响因子：
11.1
作者：
Randazzo, PA;Andrade, J;Cooper, JA
通讯作者：
Cooper, JA
影响因子：
7.2
作者：
Oeckinghaus, Andrea;Ghosh, Sankar
通讯作者：
Ghosh, Sankar
影响因子：
64.8
作者：
Rothwarf, DM;Zandi, E;Karin, M
通讯作者：
Karin, M
影响因子：
6.4
作者：
Jiang, Runqiu;Xia, Yongxiang;Sun, Beicheng
通讯作者：
Sun, Beicheng