Phosphorylation of the Stat1 transactivating domain is required for the response to type I interferons.
Stat1 (signal transducer and activator of transcription 1) regulates transcription in response to the type I interferons IFN-alpha and IFN-beta, either in its dimerized form or as a subunit of the interferon-stimulated gene factor 3 (Isgf3) complex (consisting of Stat1, Stat2 and interferon-regulating factor 9). Full-length Stat1-alpha and the splice variant Stat1-beta, which lacks the carboxyl terminus and the Ser727 phosphorylation site, are found in all cell types. IFN-induced phosphorylation of Stat1-alpha on Ser727 occurs in the absence of the candidate kinase, protein kinase C-delta. When expressed in Stat1-deficient cells, Stat1-beta and a Stat1-S727A mutant both restored the formation of Stat1 dimers and of the Isgf3 complex on treatment with IFN-beta. By contrast, only Stat1-alpha restored the ability of IFN-beta to induce high levels of transcription from target genes of Stat1 dimers and Isgf3 and to induce an antiviral state. Our data suggest an important contribution of the Stat1 C terminus and its phosphorylation at Ser727 to the transcriptional activities of the Stat1 dimer and the Isgf3 complex.
Pilz
Andreas
A
Institute of Microbiology and Genetics, Vienna Biocenter, Vienna, Austria.
Ramsauer
Katrin
K
Heidari
Hamid
H
Leitges
Michael
M
Kovarik
Pavel
P
Decker
Thomas
T
D016475:3T3 Cells; D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D000998:Antiviral Agents; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016899:Interferon-beta