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首页> 外文期刊>Nature >IKK-γ is an essential regulatory subunit of the IκB kinase complex
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IKK-γ is an essential regulatory subunit of the IκB kinase complex

机译：IKK-γ是IκB激酶复合体的重要调节亚基

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摘要

Pro-inflammatory cytokines activate the transcription factor NF-κB by stimulating the activity of a protein kinase that phosphor-ylates IκB, an inhibitor of NF-κB, at sites that trigger its ubiquitination and degradation. This results in the nuclear translocation of freed NF-κB dimers and the activation of transcription of target genes. Many of these target genes code for immunoregulatory proteins. A large, cytokine-responsive IκB kinase (IKK) complex has been purified and the genes encoding two of its subunits have been cloned. These subunits, IKK-α and IKK-β, are protein kinases whose function is needed for NF-κB activation by pro-inflammatory stimuli. Here, by using a monoclonal antibody against IKK-α, we purify the IKK complex to homogeneity from human cell lines. We find that IKK is composed of similar amounts of IKK-α, IKK-β and two other polypeptides, for which we obtained partial sequences. These polypeptides are differentially processed forms of a third subunit, IKK-γ. Molecular cloning and sequencing indicate that IKK-γ is composed of several potential coiled-coil motifs. IKK-γ interacts preferentially with IKK-β and is required for the activation of the IKK complex. An IKK-γ carboxy-terminal truncation mutant that still binds IKK-β blocks the activation of IKK and NF-κB.
机译：促炎性细胞因子通过刺激蛋白激酶的活性来激活转录因子NF-κB，该蛋白激酶在触发其泛素化和降解的位点磷酸化NF-κB抑制剂IκB。这导致释放的NF-κB二聚体的核易位并激活靶基因的转录。这些靶基因中的许多编码免疫调节蛋白。纯化了一个大型的细胞因子反应性IκB激酶（IKK）复合物，并克隆了编码其两个亚基的基因。这些亚基IKK-α和IKK-β是蛋白激酶，其功能需要通过促炎性刺激激活NF-κB。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了IKK复合物使其具有同质性。我们发现IKK由相似数量的IKK-α，IKK-β和另外两个多肽组成，为此我们获得了部分序列。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由几种潜在的卷曲螺旋基序组成。 IKK-γ优先与IKK-β相互作用，并且是IKK复合物活化所必需的。仍与IKK-β结合的IKK-γ羧基末端截短突变体阻止了IKK和NF-κB的激活。

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