Signal-induced ubiquitination of IκB kinase-β
Signal-induced ubiquitination of IκB kinase-β
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DOI：
10.1074/jbc.m310686200
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发表时间：
2003-12-05
影响因子：
4.8
通讯作者：
Ballard, DW
中科院分区：
文献类型：
--
作者：
Carter, RS;Pennington, KN;Ballard, DW
炎症和免疫遗传程序的启动涉及转录因子NF-κ B的核动员。这种信号依赖性过程部分由IkappaB激酶的β-催化亚基（IKK β）控制，IKK β标记IkappaB α和其他NF-κ B细胞质抑制剂进行蛋白水解破坏。IKK β的催化活性受到NF-κ B的病理和生理诱导剂的刺激，如Tax癌蛋白和促炎细胞因子。我们现在报告的证据表明，这些NF-κ B诱导剂靶向IKK β结合泛素（Ub）在哺乳动物细胞。修饰的IKK β的表观分子大小与单泛素化而不是多聚体Ub链的连接相容。该修饰取决于IKK β中Ser-177/Ser-181的活化T环的信号诱导磷酸化。IKK β-Ub结合物的形成在表达YopJ的细胞中被破坏，YopJ是一种干扰NF-κ B信号通路的Ub样蛋白质蛋白酶。这些发现表明磷酸化、泛素化和IKK β的生物学作用之间存在重要的机制联系。
Initiation of the genetic programs for inflammation and immunity involves nuclear mobilization of transcription factor NF-kappaB. This signal-dependent process is controlled in part by the beta-catalytic subunit of IkappaB kinase (IKKbeta), which marks IkappaBalpha and other cytoplasmic inhibitors of NF-kappaB for proteolytic destruction. The catalytic activity of IKKbeta is stimulated by pathologic and physiologic inducers of NF-kappaB, such as the Tax oncoprotein and proinflammatory cytokines. We now report evidence that these NF-kappaB inducers target IKKbeta for conjugation to ubiquitin (Ub) in mammalian cells. The apparent molecular size of modified IKKbeta is compatible with monoubiquitination rather than attachment of a multimeric Ub chain. The modification is contingent upon signal-induced phosphorylation of the activation T loop in IKKbeta at Ser-177/Ser-181. The formation of IKKbeta-Ub conjugates is disrupted in cells expressing YopJ, a Ub-like protein protease that interferes with the NF-kappaB signaling pathway. These findings indicate an important mechanistic link between phosphorylation, ubiquitination, and the biologic action of IKKbeta.