hCINAP negatively regulates NF-κB signaling by recruiting the phosphatase PP1 to deactivate IKK complex

作     者：Linglong Qu Yapeng Ji Xi Zhu Xiaofeng Zheng 

作者机构：State Key Lab of Protein and Plant Gene ResearchBeijing 100871China Department of Biochemistry and Molecular BiologySchool of Life SciencesPeking UniversityBeijing 100871China Department of Critical Care MedicinePeking University Third HospitalBeijing 100191China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2015年第7卷第6期

页      面：529-542页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学] 

基　　金：supported by the National Science Foundation of China(31170709,31470754) the Seeding Grant for Medicine and Life Sciences of Peking University(2014-MB-02) the Doctoral Fund of Ministry of Education of China(20130001130003) 

主　　题：hCINAP NF-κB IKK complex phosphatase PP1 inflammatory diseases 

摘      要：Tight regulation of nuclear factor-kB(NF-kB)signaling is essential to maintain homeostasis in immune system in response to various stimuli,which hasbeen studied extensivelyand ***,the molecularmechanisms responsible for its negative regulation are not completely *** we demonstrate that human coilin-interacting nuclear ATPase protein(hCINAP)is a novel negative regulator in NF-kB signaling by deactivating IkB kinase(IKK)*** response to TNF stimulation,hCINAP dynamically associates with IKKa and IKKb and inhibits IKK ***,hCINAP directly interacts with the catalytic subunits of protein phosphatase 1(PP1)and mediates the formation of IKK–hCINAP–PP1 complex,serving as an adaptor protein that recruits PP1 to dephosphorylate ***,decreased levels of hCINAP are observed in several inflammatory diseases with NF-kB *** study suggests a novel mechanism underlying deactivation of IKK and provides new insight into the negative regulation of NF-kB signaling.