title: Bombesin Receptor-Activated Protein (BRAP) Modulates NF-κB Activation in Bronchial Epithelial Cells by Enhancing HDAC Activity.
abstract: Our previous studies provided evidence that bombesin receptor-activated protein (BRAP), encoded by C6ORF89, is widely expressed in human airway epithelial cells and may play a role in the stress response of lung epithelia. In this study, we demonstrated that BRAP has a regulatory effect on NF-κB transcriptional activity in cultured human bronchial epithelial cells (HBECs). BRAP overexpression by gene transfer inhibited both basal and inducible NF-κB transcriptional activity in HBECs, whereas BRAP knockdown had the opposite effect. BRAP was shown to regulate NF-κB activity by enhancing histone deacetylase (HDAC) activity. In addition, BRAP might increase HDAC activity that leads to NF-κB activation via its putative C-terminal domain. Our study suggests that the BRAP protein is an important regulator of immune and inflammatory responses in the human airway epithelium.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Qin
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Section of Gastroenterology, Boston, 02118, Massachusetts.
authors.forename: Horst Christian
authors.initials: HC
authors.lastname: Weber
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Qu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D010083:Oxidants, Photochemical / Q000494:pharmacology; D010126:Ozone / Q000494:pharmacology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D010083:Oxidants, Photochemical; D017382:Reactive Oxygen Species; D010126:Ozone; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: BOMBESIN RECEPTOR-ACTIVATED PROTEIN; BRONCHIAL EPITHELIAL CELLS; HISTONE DEACETYLASE; NF-κB