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Mechanisms of transcriptional activation of the stimulator of interferon genes by
transcription factors CREB and c-Myc
#MMPMID27835584
Wang YY
; Jin R
; Zhou GP
; Xu HG
Oncotarget
2016[Dec]; 7
(51
): 85049-85057
PMID27835584
show ga
Stimulator of interferon genes (STING) plays an important role in host defense,
autoimmune disease, osteoclast differentiation and anti-tumor response. Although
many downstream targets have been studied in depth, the regulation of STING gene
expression remains largely unknown. Here we demonstrate that transcription
factors CREB and c-Myc maintain the transcriptional activity of STING. By
5'-rapid amplification of cDNA ends analysis, we identified the transcriptional
start site (TSS) of STING. We illustrated that the region -124/+1 relative to TSS
was sufficient for full promoter activity by a series of 5' deletion promoter
constructs. Transcriptional activity of the STING minimal promoter was dependent
on CREB and c-Myc binding motifs and was abolished after mutation of these two
DNA elements. Chromatin immunoprecipitation assays demonstrated that
transcription factors CREB and c-Myc bind to STING promoter in vivo.
Overexpression of CREB and c-Myc increased the STING promoter activity.
Meanwhile, knocking-down of CREB and c-Myc by a small interfering RNA (siRNA)
strategy markedly reduced endogenous STING expression. In summary, these results
demonstrated that transcription factors CREB and c-Myc are involved in the
regulation of STING transcription.
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