NF-κB通路的机理解释(英文维基百科之翻译).docx

Inhibition[/w/index.php?title=NF-%CE%BABaction=editsection=7edit]In unstimulated cells, the NF-κB dimers are sequestered in the?/wiki/Cytoplasmcytoplasm?by a family of inhibitors, called IκBs (Inhibitor of κB), which are proteins that contain multiple copies of a sequence called ankyrin repeats. By virtue of their ankyrin repeat domains, the IκB proteins mask the?/wiki/Nuclear_localization_signalnuclear localization signals(NLS) of NF-κB proteins and keep them sequestered in an inactive state in the cytoplasm./wiki/NF-%CE%BAB[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?/wiki/PEST_sequencePEST domain?near their C terminus. Although the IκB family consists of?/wiki/I%CE%BAB%CE%B1IκBα,?/wiki/NFKBIBIκBβ,?/wiki/NFKBIEIκBε, and?/wiki/BCL3Bcl-3, the best-studied and major IκB protein is IκBα. Due to the presence 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 functions as an inhibitor./wiki/NF-%CE%BAB[29]/wiki/NF-%CE%BAB[30]?IκBδ degradation in response to developmental stimuli, such as those transduced through?/wiki/Lymphotoxin_beta_receptorLTβR, potentiate NF-κB dimer activation in a NIK dependent non-canonical pathway./wiki/NF-%CE%BAB[29]/wiki/NF-%CE%BAB[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。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 kinase called the?/wiki/I%CE%BAB_kinaseIκB kinase?(IKK). IKK is composed of a heterodimer of the catalytic IKKα and IKKβ subunits and a ma