Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts
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, d...
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Online Access: | https://hdl.handle.net/10037/6805 https://doi.org/10.1016/j.fob.2014.09.007 |
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ftunivtroemsoe:oai:munin.uit.no:10037/6805 2023-05-15T15:31:54+02:00 Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts Sobhkhez, Mehrdad Skjesol, Astrid Thomassen, Ernst Ivan Iliev, Dimitar Borisov Sun, Baojian Robertsen, Børre Jørgensen, Jorunn B 2014 https://hdl.handle.net/10037/6805 https://doi.org/10.1016/j.fob.2014.09.007 eng eng Elsevier FEBS Open Bio 4(2014) s. 858-871 FRIDAID 1167898 doi:10.1016/j.fob.2014.09.007 http://dx.doi.org/10.1016/j.fob.2014.09.007 2211-5463 https://hdl.handle.net/10037/6805 URN:NBN:no-uit_munin_6404 openAccess VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 Atlantic salmon STAT2 IRF9 IFN Fish Journal article Tidsskriftartikkel Peer reviewed 2014 ftunivtroemsoe https://doi.org/10.1016/j.fob.2014.09.007 2021-06-25T17:54:03Z 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. Article in Journal/Newspaper Atlantic salmon Salmo salar University of Tromsø: Munin Open Research Archive FEBS Open Bio 4 1 858 871 |
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Open Polar |
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University of Tromsø: Munin Open Research Archive |
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ftunivtroemsoe |
language |
English |
topic |
VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 Atlantic salmon STAT2 IRF9 IFN Fish |
spellingShingle |
VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 Atlantic salmon STAT2 IRF9 IFN Fish Sobhkhez, Mehrdad Skjesol, Astrid Thomassen, Ernst Ivan Iliev, Dimitar Borisov Sun, Baojian Robertsen, Børre Jørgensen, Jorunn B Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts |
topic_facet |
VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 Atlantic salmon STAT2 IRF9 IFN Fish |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Sobhkhez, Mehrdad Skjesol, Astrid Thomassen, Ernst Ivan Iliev, Dimitar Borisov Sun, Baojian Robertsen, Børre Jørgensen, Jorunn B |
author_facet |
Sobhkhez, Mehrdad Skjesol, Astrid Thomassen, Ernst Ivan Iliev, Dimitar Borisov Sun, Baojian Robertsen, Børre Jørgensen, Jorunn B |
author_sort |
Sobhkhez, Mehrdad |
title |
Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts |
title_short |
Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts |
title_full |
Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts |
title_fullStr |
Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts |
title_full_unstemmed |
Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts |
title_sort |
structural and functional characterization of salmon stat1, stat2 and irf9 homologs sheds light on interferon signaling in teleosts |
publisher |
Elsevier |
publishDate |
2014 |
url |
https://hdl.handle.net/10037/6805 https://doi.org/10.1016/j.fob.2014.09.007 |
genre |
Atlantic salmon Salmo salar |
genre_facet |
Atlantic salmon Salmo salar |
op_relation |
FEBS Open Bio 4(2014) s. 858-871 FRIDAID 1167898 doi:10.1016/j.fob.2014.09.007 http://dx.doi.org/10.1016/j.fob.2014.09.007 2211-5463 https://hdl.handle.net/10037/6805 URN:NBN:no-uit_munin_6404 |
op_rights |
openAccess |
op_doi |
https://doi.org/10.1016/j.fob.2014.09.007 |
container_title |
FEBS Open Bio |
container_volume |
4 |
container_issue |
1 |
container_start_page |
858 |
op_container_end_page |
871 |
_version_ |
1766362394880114688 |