Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1.
Despite rapid progress in elucidating the molecular mechanisms of activation of the kinase IKK, the processes that regulate IKK deactivation are still unknown. Here we demonstrate that CUE domain-containing 2 (CUEDC2) interacted with IKKalpha and IKKbeta and repressed activation of the transcription factor NF-kappaB by decreasing phosphorylation and activation of ... IKK. Notably, CUEDC2 also interacted with GADD34, a regulatory subunit of protein phosphatase 1 (PP1). We found that IKK, CUEDC2 and PP1 existed in a complex and that IKK was released from the complex in response to inflammatory stimuli such as tumor necrosis factor. CUEDC2 deactivated IKK by recruiting PP1 to the complex. Therefore, CUEDC2 acts as an adaptor protein to target IKK for dephosphorylation and inactivation by recruiting PP1.
Mesh Terms:
Animals, Antigens, Differentiation, Carrier Proteins, Catalytic Domain, Cell Cycle Proteins, Cells, Cultured, Female, Humans, I-kappa B Kinase, Inflammation, Interleukin-6, Macrophages, Membrane Proteins, Mice, Mice, Inbred C57BL, NF-kappa B, Phosphorylation, Protein Binding, Protein Phosphatase 1, Up-Regulation
Animals, Antigens, Differentiation, Carrier Proteins, Catalytic Domain, Cell Cycle Proteins, Cells, Cultured, Female, Humans, I-kappa B Kinase, Inflammation, Interleukin-6, Macrophages, Membrane Proteins, Mice, Mice, Inbred C57BL, NF-kappa B, Phosphorylation, Protein Binding, Protein Phosphatase 1, Up-Regulation
Nat. Immunol.
Date: May. 01, 2008
PubMed ID: 18362886
View in: Pubmed Google Scholar
Download Curated Data For This Publication
112565
Switch View:
- Interactions 11