Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1

Hui Yan Li; Hui Liu; Chen Hui Wang; Ji Yan Zhang; Jiang Hong Man; Yan Fei Gao; Pei Jing Zhang; Wei Hua Li; Jie Zhao; Xin Pan; Tao Zhou; Wei Li Gong; Ai Ling Li; Xue Min Zhang

doi:10.1038/ni.1600

Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1

Hui Yan Li, Hui Liu, Chen Hui Wang, Ji Yan Zhang, Jiang Hong Man, Yan Fei Gao, Pei Jing Zhang, Wei Hua Li, Jie Zhao, Xin Pan, Tao Zhou, Wei Li Gong, Ai Ling Li, Xue Min Zhang

Experimental Radiation Oncology

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

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 IKKα and IKKβ and repressed activation of the transcription factor NF-κB 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.

Original language	English (US)
Pages (from-to)	533-541
Number of pages	9
Journal	Nature Immunology
Volume	9
Issue number	5
DOIs	https://doi.org/10.1038/ni.1600
State	Published - May 2008

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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@article{c4f748a293c2451287676b9ae8cf048e,

title = "Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1",

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 IKKα and IKKβ and repressed activation of the transcription factor NF-κB 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.",

author = "Li, {Hui Yan} and Hui Liu and Wang, {Chen Hui} and Zhang, {Ji Yan} and Man, {Jiang Hong} and Gao, {Yan Fei} and Zhang, {Pei Jing} and Li, {Wei Hua} and Jie Zhao and Xin Pan and Tao Zhou and Gong, {Wei Li} and Li, {Ai Ling} and Zhang, {Xue Min}",

note = "Funding Information: We thank Z.G. Liu (National Cancer Institute, National Institutes of Health) for human IKKa and IKKb plasmids and TRAF2-deficient MEFs; M.W. Mayo (University of Virginia) for the p65 expression plasmid; X. Lin (Anderson Cancer Center) for the RIP expression vector; X.X. Li (Cleveland Clinic Foundation) for construction of pE-selectin-Luc; G. Haegeman (University of Gent, Gent) for the pIL-6-Luc plasmid; and Z.G. Liu for discussions and technical help. Supported by the National Natural Science Foundation of China (30525021, 30672357, 30500583 and 30321003), the Major State Basic Research Development Program of China (973 Program; 2004CB518800) and the National High Technology Research and Development Program of China (2006AA02Z340).",

year = "2008",

month = may,

doi = "10.1038/ni.1600",

language = "English (US)",

volume = "9",

pages = "533--541",

journal = "Nature Immunology",

issn = "1529-2908",

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T1 - Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1

AU - Li, Hui Yan

AU - Liu, Hui

AU - Wang, Chen Hui

AU - Zhang, Ji Yan

AU - Man, Jiang Hong

AU - Gao, Yan Fei

AU - Zhang, Pei Jing

AU - Li, Wei Hua

AU - Zhao, Jie

AU - Pan, Xin

AU - Zhou, Tao

AU - Gong, Wei Li

AU - Li, Ai Ling

AU - Zhang, Xue Min

N1 - Funding Information: We thank Z.G. Liu (National Cancer Institute, National Institutes of Health) for human IKKa and IKKb plasmids and TRAF2-deficient MEFs; M.W. Mayo (University of Virginia) for the p65 expression plasmid; X. Lin (Anderson Cancer Center) for the RIP expression vector; X.X. Li (Cleveland Clinic Foundation) for construction of pE-selectin-Luc; G. Haegeman (University of Gent, Gent) for the pIL-6-Luc plasmid; and Z.G. Liu for discussions and technical help. Supported by the National Natural Science Foundation of China (30525021, 30672357, 30500583 and 30321003), the Major State Basic Research Development Program of China (973 Program; 2004CB518800) and the National High Technology Research and Development Program of China (2006AA02Z340).

PY - 2008/5

Y1 - 2008/5

N2 - 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 IKKα and IKKβ and repressed activation of the transcription factor NF-κB 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.

AB - 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 IKKα and IKKβ and repressed activation of the transcription factor NF-κB 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.

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Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1

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