| Autor: |
Bradley J. Ungurait, Robert S. Carter, Pia Arrate, Dean W. Ballard, Kevin N. Pennington |
| Rok vydání: |
2003 |
| Předmět: |
|
| Zdroj: |
Journal of Biological Chemistry. 278:48903-48906 |
| ISSN: |
0021-9258 |
| Popis: |
Initiation of the genetic programs for inflammation and immunity involves nuclear mobilization of transcription factor NF-κB. This signal-dependent process is controlled in part by the β-catalytic subunit of IκB kinase (IKKβ), which marks IκBα and other cytoplasmic inhibitors of NF-κB for proteolytic destruction. The catalytic activity of IKKβ is stimulated by pathologic and physiologic inducers of NF-κB, such as the Tax oncoprotein and proinflammatory cytokines. We now report evidence that these NF-κB inducers target IKKβ for conjugation to ubiquitin (Ub) in mammalian cells. The apparent molecular size of modified IKKβ 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 IKKβ at Ser-177/Ser-181. The formation of IKKβ-Ub conjugates is disrupted in cells expressing YopJ, a Ub-like protein protease that interferes with the NF-κB signaling pathway. These findings indicate an important mechanistic link between phosphorylation, ubiquitination, and the biologic action of IKKβ. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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