Stabilization of RelB requires multidomain interactions with p100/p52
Stabilization of RelB requires multidomain interactions with p100/p52
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DOI：
10.1074/jbc.m707898200
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发表时间：
2008-05-02
影响因子：
4.8
通讯作者：
Ghosh, Gourisankar
中科院分区：
文献类型：
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作者：
Fusco, Amanda J.;Savinova, Olga V.;Ghosh, Gourisankar
NF-kappa B家族成员RelB具有许多其他家族成员所不具有的特性，如限制性亚基结合和缺乏经典I kappa B蛋白的调控。我们发现，在p100缺失的情况下，RelB蛋白水平显著降低，而在p100和p105缺失的情况下，RelB蛋白水平的降低幅度更大。RelB通过直接与p100、p105及其加工产物相互作用来稳定自身。然而，RelB通过不同的相互作用模式与它的伙伴形成复合物。尽管p105的c端锚蛋白重复结构域不参与RelB-p105复合物的形成，但每种蛋白的所有结构域和柔性区域都参与RelB-p100复合物的形成。在一些方面，RelB-p52和RelB-p100复合物在NF-kappa B家族中是独特的。p100/p52的n端结构域与RelB相互作用，而不与RelA相互作用。RelB的转录激活域，而不是RelA，直接与p100的加工区域相互作用。这些独特的蛋白-蛋白接触解释了为什么RelB倾向于将p52作为其转录活性的二聚体伙伴，并作为p100抑制复合物保留在细胞质中。这种关联介导的RelB稳定意味着RelB可能在p100向p52的加工过程中发挥作用。
The NF-kappa B family member RelB has many properties not shared by other family members such as restricted subunit association and lack of regulation by the classical I kappa B proteins. We show that the protein level of RelB is significantly reduced in the absence of p100 and reduced even more when both p100 and p105 are absent. RelB stabilizes itself by directly interacting with p100, p105, and their processed products. However, RelB forms complexes with its partners using different interaction modes. Although the C-terminal ankyrin repeat domain of p105 is not involved in the RelB-p105 complex formation, all domains and flexible regions of each protein are engaged in the RelB-p100 complex. In several respects the RelB-p52 and RelB-p100 complexes are unique in the NF-kappa B family. The N-terminal domain of p100/p52 interacts with RelB but not RelA. The transcriptional activation domain of RelB, but not RelA, directly interacts with the processing region of p100. These unique protein-protein contacts explain why RelB prefers p52 as its dimeric partner for transcriptional activity and is retained in the cytoplasm as an inhibited complex by p100. This association-mediated stabilization of RelB implies a possible role for RelB in the processing of p100 into p52.