title: Negative feedback regulation of NF-κB action by CITED2 in the nucleus.
abstract: NF-κB is a family of important transcription factors that modulate immunity, development, inflammation, and cancer. The biological activity of NF-κB is subjected to various spatial and temporal regulations. Bioinformatics analysis predicts that CITED2 is topologically close to NF-κB in the protein interaction networks. In this study, we show that ectopic expression or knockdown of CITED2 attenuates or potentiates, respectively, the expression of NF-κB-responsive genes. Mechanistically, CITED2 constitutively localizes inside the nucleus and interacts specifically with the coactivator p300. This prevents p65 from binding to p300, impairs p65 acetylation, and attenuates p65 binding to its cognate promoters. Furthermore, LPS induces CITED2 expression via NF-κB in macrophages. CITED2 sensitizes cells to TNF-α-induced apoptosis. Collectively, this study identifies CITED2 as a novel regulator of NF-κB in the nucleus, which reveals a negative feedback mechanism for NF-κB signaling.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Lou
authors.forename: Shaogang
authors.initials: S
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Huang
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Yufei
authors.initials: Y
authors.lastname: Shan
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D025461:Feedback, Physiological / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D025941:Protein Interaction Mapping; D012097:Repressor Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*
chemical_list: C486381:CITED2 protein, human; C110087:Cited2 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012097:Repressor Proteins; D015534:Trans-Activators