The DEAD-Box RNA Helicase DDX3 Interacts with NF-?B 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)-?B subunit p65 and suppresses NF-?B (p65/p50)-mediated transcriptional activity. The downregulation of DDX3 by RNA interference induces the upregulation of NF-?B (p65/p50)-mediated transcription. The regulation of NF-?B (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-?B-regulated gene transcription. In summary, the results suggest that DDX3 functions to suppress the transcriptional activity of the NF-?B subunit p65.

SUBMITTER: Xiang N 

PROVIDER: S-EPMC5063347 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature