title: The DEAD-Box RNA Helicase DDX3 Interacts with NF-κB Subunit p65 and Suppresses p65-Mediated Transcription.
abstract: RNA helicase family members exhibit diverse cellular functions, including in transcription, pre-mRNA processing, RNA decay, ribosome biogenesis, RNA export and translation. The RNA helicase DEAD-box family member DDX3 has been characterized as a tumour-associated factor and a transcriptional co-activator/regulator. Here, we demonstrate that DDX3 interacts with the nuclear factor (NF)-κB subunit p65 and suppresses NF-κB (p65/p50)-mediated transcriptional activity. The downregulation of DDX3 by RNA interference induces the upregulation of NF-κB (p65/p50)-mediated transcription. The regulation of NF-κB (p65/p50)-mediated transcriptional activity was further confirmed by the expression levels of its downstream cytokines, such as IL-6 and IL-8. Moreover, the binding of the ATP-dependent RNA helicase domain of DDX3 to the N-terminal Rel homology domain (RHD) of p65 is involved in the inhibition of NF-κB-regulated gene transcription. In summary, the results suggest that DDX3 functions to suppress the transcriptional activity of the NF-κB subunit p65.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Musarat
authors.initials: M
authors.lastname: Ishaq
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Song
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Guihong
authors.initials: G
authors.lastname: Sun
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.|School of Basic Medical Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors.forename: Yu
authors.identifier: http://orcid.org/0000-0003-1300-4652
authors.initials: Y
authors.lastname: Chen
mesh_terms: D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D017930:Genes, Reporter; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases