IKK-γ is an essential regulatory subunit of the IκB kinase complex
IKK-γ is an essential regulatory subunit of the IκB kinase complex
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作者：
Rothwarf, DM;Zandi, E;Karin, M
促炎细胞因子通过刺激蛋白激酶的活性激活转录因子NF-κ B，该蛋白激酶磷酸化I κ B，NF-κ B1-5的抑制剂，af位点触发其泛素化和降解。这导致游离的NF-κ B二聚体的核转位和靶基因转录的激活（6，7）。这些靶基因中的许多编码免疫调节蛋白（8，9）。已纯化了一种大的、对精氨酸敏感的I κ B激酶（IKK）复合物，并克隆了编码其两个亚基的基因（1、2、5）。这些亚基IKK-α和IKK-β是蛋白激酶，其功能是促炎刺激激活NF-κ B所需的。在这里，通过使用针对IKK-α的单克隆抗体，我们从人细胞系中纯化IKK复合物至同质。我们发现IKK由相似量的IKK-α、IKK-β和另外两种多肽组成，我们获得了它们的部分序列。这些多肽是第三亚基IKK-γ的差异加工形式。分子克隆和测序表明，IKK-γ是由几个潜在的卷曲螺旋蛾。IKK-γ优先与IKK-β相互作用，并且是IKK复合物激活所必需的。仍然结合IKK-β的IKK-γ羧基末端截短突变体阻断IKK和NF-κ B的活化。
Pro-inflammatory cytokines activate the transcription factor NF-kappa B by stimulating the activity of a protein kinase that phosphorylates I kappa B, an inhibitor of NF-kappa B1-5, af sites that trigger its ubiquitination and degradation. This results in the nuclear translocation of freed NF-kappa B dimers and the activation of transcription of target genes(6,7). Many of these target genes code for immunoregulatory proteins(8,9). A large, cytokine-responsive I kappa B kinase (IKK) complex has been purified and the genes encoding two of its subunits have been cloned(1,2,5). These subunits, IKK-alpha and IKK-beta, are protein kinases whose function is needed for NF-kappa B activation by pro-inflammatory stimuli. Here, by using a monoclonal antibody against IKK-alpha, we purify the IKK complex to homogeneity from human cell lines. We find that IKK is composed of similar amounts of IKK-alpha, IKK-beta and two other polypeptides, for which we obtained partial sequences. These polypeptides are differentially processed forms of a third subunit, IKK-gamma. Molecular cloning and sequencing indicate that IKK-gamma is composed of several potential coiled-coil moths. IKK-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex. An IKK-gamma carboxy-terminal truncation mutant that still binds IKK-beta blocks the activation of IKK and NF-kappa B.