hCINAP negatively regulates NF-κB signaling by recruiting the phosphatase PP1 to deactivate IKK complex
hCINAP 否定地调整由招募发信号的 NF-B 撤销的磷酸酶 PP1 IKK 建筑群作者机构: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.