Identification of TRAIL as an interferon regulatory factor 3 transcriptional target.
Interferon production and apoptosis in virus-infected cells are necessary to prevent progeny virus production and to eliminate infected cells. Paramyxovirus infection induces apoptosis through interferon regulatory factor 3 (IRF-3), but the exact mechanism of how IRF-3 functions is unknown. We show that IRF-3 is involved in the transcriptional induction of TRAIL, a key player in the apoptosis pathway. IRF-3 upregulates TRAIL transcription following viral infection and binds an interferon-stimulated response element in the TRAIL promoter. The mRNA for TRAIL and its receptor, DR5, are induced following viral infection. These studies identify TRAIL as a novel IRF-3 transcriptional target.
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Jessica R
JR
Kirshner
Alla Y
AY
Karpova
Maren
M
Kops
Peter M
PM
Howley
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D029082:Sendai virus / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha