Identification of F-box only protein 7 as a negative regulator of NF-kappaB signalling.

Identification of F-box only protein 7 as a negative regulator of NF-kappaB signalling.
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DOI:
10.1111/j.1582-4934.2012.01524.x
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发表时间:
2012-09
影响因子:
5.3
通讯作者:
Dirac AM
Dirac AM
中科院分区:
医学2区
文献类型:
--
作者:
Kuiken HJ;Egan DA;Laman H;Bernards R;Beijersbergen RL;Dirac AM

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核因子κB(NF-κB)信号通路控制重要的细胞事件,如细胞增殖、分化、凋亡和免疫应答。通路激活在TNFα刺激后迅速发生,并且高度依赖于泛素化事件。使用NF-κB转录因子家族成员p65的细胞质至细胞核的易位作为读数,我们筛选了靶向参与泛素缀合和去缀合的酶的合成siRNA文库,用于NF-κB信号传导中调节泛素化事件的修饰剂。我们鉴定了F-box protein only 7(FBXO 7),它是Skp,Cullin,F-box(SCF)-泛素连接酶复合物的一个组分,是NF-κB信号传导的负调节因子。F-box蛋白仅7结合并介导泛素与cIAP 1和TRAF 2结合,导致RIP 1泛素化减少和NF-κB信号传导活性降低。
The nuclear factor κB (NF-κB) signalling pathway controls important cellular events such as cell proliferation, differentiation, apoptosis and immune responses. Pathway activation occurs rapidly upon TNFα stimulation and is highly dependent on ubiquitination events. Using cytoplasmic to nuclear translocation of the NF-κB transcription factor family member p65 as a read-out, we screened a synthetic siRNA library targeting enzymes involved in ubiquitin conjugation and de-conjugation for modifiers of regulatory ubiquitination events in NF-κB signalling. We identified F-box protein only 7 (FBXO7), a component of Skp, Cullin, F-box (SCF)-ubiquitin ligase complexes, as a negative regulator of NF-κB signalling. F-box protein only 7 binds to, and mediates ubiquitin conjugation to cIAP1 and TRAF2, resulting in decreased RIP1 ubiquitination and lowered NF-κB signalling activity.
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