Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts. Issue 1 (7th October 2014)

• Record Type: Journal Article
• Authors: Sobhkhez, Mehrdad; Skjesol, Astrid; Thomassen, Ernst; Tollersrud, Linn Greiner; Iliev, Dimitar B.; Sun, Baojian; Robertsen, Børre; Jørgensen, Jorunn B.
• Is Part Of: FEBS open bio. Volume 4:Issue 1(2014)
• Page Start: 858
• Page End: 871
• Publication Date: 2014-10-07
• Subjects: Atlantic salmon -- STAT2 -- IRF9 -- IFN -- Fish; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.fob.2014.09.007
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Mammalian IRF9 and STAT2, together with STAT1, form the ISGF3 transcription factor complex, which is critical for type I interferon (IFN)‐induced signaling, while IFNγ stimulation is mediated by homodimeric STAT1 protein. Teleost fish are known to possess most JAK and STAT family members, however, description of their functional activity in lower vertebrates is still scarce. In the present study we have identified two different STAT2 homologs and one IRF9 homolog from Atlantic salmon ( Salmo salar ). Both proteins have domain‐like structures with functional motifs that are similar to higher vertebrates, suggesting that they are orthologs to mammalian STAT2 and IRF9. The two identified salmon STAT2s, named STAT2a and STAT2b, showed high sequence identity but were divergent in their transactivation domain (TAD). Like STAT1, ectopically expressed STAT2a and b were shown to be tyrosine phosphorylated by type I IFNs and, interestingly, also by IFNγ. Microscopy analyses demonstrated that STAT2 co‐localized with STAT1a in the cytoplasm of unstimulated cells, while IFNa1 and IFNγ stimulation seemed to favor their nuclear localization. Overexpression of STAT2a or STAT2b together with STAT1a activated a GAS‐containing reporter gene construct in IFNγ‐stimulated cells. The highest induction of GAS promoter activation was found in IFNγ‐stimulated cells transfected with IRF9 alone. Taken together, these data suggest that salmon STAT2 and IRF9 may have a role in IFNγ‐induced signaling and promote the expression of GAS‐driven genes in bony fish. Since mammalian STAT2 is primarily an ISGF3 component and not involved in IFNγ signaling, our finding features a novel role for STAT2 in fish. Abstract : The transcription factors STAT2 and IRF9 from Atlantic salmon have been identified. STAT2 co‐expressed with STAT1 translocates to the nucleus upon IFN stimulation. STAT2 are tyrosine phosphorylated upon type I IFN and IFNγ stimulation. STAT2 and STAT1, as well as IRF9, activates GAS elements upon IFNγ stimulation. Our results suggest novel roles of salmon STAT2 and IRF9 in IFNγ‐mediated signaling.