Article abstract
Nature Immunology 9, 533 - 541 (2008)
Published online: 23 March 2008 | doi:10.1038/ni.1600
Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1
Hui-Yan Li1,2, Hui Liu1,2, Chen-Hui Wang1, Ji-Yan Zhang1, Jiang-Hong Man1, Yan-Fei Gao1, Pei-Jing Zhang1, Wei-Hua Li1, Jie Zhao1, Xin Pan1, Tao Zhou1, Wei-Li Gong1, Ai-Ling Li1 & Xue-Min Zhang1
Abstract
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 IKK
and IKK
and repressed activation of the transcription factor NF-
B 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.
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
- These authors contributed equally to this work.
Correspondence to: Xue-Min Zhang1 e-mail: xmzhang@nic.bmi.ac.cn
Correspondence to: Ai-Ling Li1 e-mail: lal@proteomics.cn
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