Inhibition[edit]
In unstimulated cells, the NF-κB dimers are questered in the cytoplasm by a family of inhibitors, called IκBs (Inhibitor of κB), which are proteins that contain multiple copies of a quence called ankyrin repeats. By virtue of their ankyrin repeat domains, the IκB proteins mask the nuclear localization signals(NLS) of NF-κB proteins and keep them questered in an inactive state in the cytoplasm.离骨散[28]
在未刺激的细胞的细胞质中，一种名为IκBs（κB的抑制剂）可以阻断NF-κB二聚体，IκBs是一种含有多个拷贝名为锚蛋白重复序列的蛋白。由于锚蛋白重复序列的结构域，IκB蛋白会掩盖NF-κB蛋白核定位信号，并且在细胞质中使它们保持一种未激活的状态。
IκBs are a family of related proteins that have an N-terminal regulatory domain, followed by six or more ankyrin repeats and a PEST domain near their C terminus. Although the IκB family consists of IκBα, IκBβ, IκBε, and Bcl-3, the best-studied and major IκB protein is IκBα. Due to the prence of ankyrin repeats in their C-terminal halves, p105 and p100 also function as IκB proteins. The c-terminal half of p100, that is often referred to as IκBδ, also f
unctions as an inhibitor.[29][30] IκBδ degradation in respon to developmental stimuli, such as tho transduced through LTβR, potentiate NF-κB dimer activation in a NIK dependent non-canonical pathway.[29][31]
IκBs是有着N端基调解域的相关蛋白一个家族，在C端基附近有着6个或者更多锚蛋白重复序列和PEST结构域。虽然IκB家族包括IκBα, IκBβ, IκBε, and Bcl-3，研究最多和主要的IκB蛋白就是IκBα。因为它们C端基锚蛋白重复序列的存在，p105和p100起到了IκB蛋白的功能吡格列酮二甲双胍片。p100C端基的一半，就是常称作是IκBδ，也起到了抑制的作用。IκBδ的下调对刺激有着应答，如通过LTβR的转换信号，以依赖于NIK的非经典通路二增强NF-κB二聚体的活性。
Activation of the NF-κB is initiated by the signal-induced degradation of IκB proteins. This occurs primarily via activation of a kina called the IκB kina (IKK). IKK is compod of a heterodimer of the catalytic IKKα and IKKβ subunits and a "master" regulatory protein termed NEMO (NF-κB esntial modulator) or IKK gamma. When activated by signals, usually coming from the outside of the cell, the IκB kina phosphorylates two rine resi
dues located in an IκB regulatory domain. When phosphorylated on the rines (e.g., rines 32 and 36 in human IκBα), the IκB inhibitor molecules are modified by a process called ubiquitination, which then leads them to be degraded by a cell structure called the proteasome.
NF-κB的激活由IκB蛋白信号诱导的降解的发起的。这主要通过一种激酶也就是IκB激酶（IKK）的激活。IKK由IKKα、IKKβ亚基和一种“主要的”NEMO（NF-κB基本调节器）或IKKγ调节蛋白组成的异质二聚体。一旦其中的丝氨酸发生磷酸化，例如在人的IκBα丝氨酸32和36，泛素化的过程起着修饰IκB抑制剂分子。一种细胞结构名为蛋白酶体可以导致抑制剂发生降解。
With the degradation of IκB, the NF-κB complex is then freed to enter the nucleus where it can 'turn on' the expression of specific genes that have DNA-binding sites for NF-κB nearby. The activation of the genes by NF-κB then leads to the given physiological respon, for example, an inflammatory or immune respon, a cell survival respon, or cellular proliferation. NF-κB turns on expression of its own repressor, IκBα. The newly syn
thesized IκBα then re-inhibits NF-κB and, thus, forms an auto feedback loop, which results in oscillating levels of NF-κB activity.[32]
伴随着IκB降解，NF-κB复合物可以自由进入细胞核，在核中因为NF-κB在附近，复合物可以启动有着DNA结合位点的特异基因的表达。通过NF-κB激活的基因随后导致给定的生理反应，举例来说，一个炎症或免疫反应，一个细胞存活反应或者细胞的增殖。NF-κB启动它自身抑制剂-IκBα的表达。新合成的IκBα然后再抑制NF-κB，因此，组成一个自动反馈回路，引起NF-κB活力的水平的振荡。
In addition, veral virus, including the AIDS virus HIV, have binding sites for NF-κB that controls the expression of viral genes, which in turn contribute to viral replication or viral pathogenicity. In the ca of HIV-1, activation of NF-κB may, at least in part, be involved in activation of the virus from a latent, inactive state.[33] YopP is a factor creted by 微波炉加热Yersinia pestis, the causative agent of plague, that prevents the ubiquitination of IκB. This caus this pathogen to effectively inhibit the NF-κB pathway and thus block the immune respon of a human infected with Yersinia.[34]
另外，有一些病毒，包括AIDS病毒HIV，有着控制病毒基因表达的NF-κB的结合位点，反过来有助于病毒复制或病毒的病理性。在HIV-1的情况下，NF-κB的活化，至少在某种程度上，
拉萨犬As a drug target[学做油条edit]
Aberrant activation of NF-κB is frequently obrved in many cancers. Moreover, suppression of NF-κB limits the proliferation of cancer cells. In addition, NF-κB is a key player in the inflammatory respon. Hence methods of inhibiting NF-κB signaling has potential therapeutic application in cancer and inflammatory dias.[71][72]
The discovery that activation of NF-κB nuclear translocation can be parated from the elevation of oxidant stress[73] gives an important hint to the development of strategies for NF-κB inhibition.
A new drug called denosumab 画简笔画acts to rai bone mineral density and reduce fracture rates in many patient sub-groups by inhibiting像我这样迷茫的人 RANKL. RANKL acts through its receptor R
沙漠玫瑰叶子发黄是怎么回事
ANK, which in turn promotes NF-κB,[74] RANKL normally works by enabling the differentiation of osteoclasts from monocytes.
Disulfiram, olmesartan and dithiocarbamates can inhibit the nuclear factor-κB (NF-κB) signaling cascade.[75]
Anatabine's antiinflammatory effects are claimed to result from modulation of NF-κB activity.[76] However the studies purporting its benefit u abnormally high dos in the millimolar range (similar to the extracellular potassium concentration), which are unlikely to be achieved in humans.
