title: E3 ubiquitin ligase Cbl-b suppresses human ORMDL3 expression through STAT6 mediation.
abstract: Orosomucoid 1-Like Protein 3 (ORMDL3) is an asthma candidate gene and Casitas B lineage lymphoma b (Cbl-b), an E3 ubiquitin ligase, is a critical factor in maintaining airway immune tolerance. However, the association of Cbl-b with ORMDL3 for asthma is unclear. Here, we show that expression of ORMDL3 is significantly increased and shows a strong linear correlation with decreased Cbl-b in the peripheral blood of recurrent wheeze patients. To elucidate the molecular mechanisms underlying this correlation, we identified that Cbl-b suppressed the transcriptional activity and mRNA expression of ORMDL3 in vivo. Further investigation showed that phosphorylation of signal transducer and activator of transcription 6 (STAT6) was induced by interleukin 4 bound to the ORMDL3 promoter, while Cbl-b reduced the phosphorylation of STAT6. Our results show that Cbl-b suppresses human ORMDL3 expression through STAT6.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Pediatrics, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province 310006, China.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shu
authors.affiliation: Department of Respiratory, Wuxi Children's Hospital, Wuxi, Jiangsu Province 214023, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Liang-Hua
authors.initials: LH
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhuang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China. Electronic address: gpzhou2015@163.com.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C464399:ORMDL3 protein, human; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl
keywords: Casitas B lineage lymphoma b; Orosomucoid 1-Like Protein 3; Signal transducer and activator of transcription 6; Transcriptional regulation; Wheeze