Ubiquitin-specific protease 13 regulates IFN signaling by stabilizing STAT1

The IFN immune system comprises type I, II, and III IFNs, signals through the JAK-STAT pathway, and plays central roles in host defense against viral infection. Posttranslational modifications such as ubiquitination regulate diverse molecules in the IFN pathway. To search for the deubiquitinating en...

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Published inThe Journal of immunology (1950) Vol. 191; no. 6; pp. 3328 - 3336
Main Authors Yeh, Hom-Ming, Yu, Chia-Yi, Yang, Ho-Chun, Ko, Shih-Han, Liao, Ching-Len, Lin, Yi-Ling
Format Journal Article
LanguageEnglish
Published United States 15.09.2013
Subjects
Blotting, Western
Dengue virus
Dengue Virus - immunology
Endopeptidases - immunology
Endopeptidases - metabolism
Fluorescent Antibody Technique
Humans
Immunoprecipitation
Interferons - immunology
Interferons - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction - immunology
STAT1 Transcription Factor - immunology
STAT1 Transcription Factor - metabolism
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Summary:The IFN immune system comprises type I, II, and III IFNs, signals through the JAK-STAT pathway, and plays central roles in host defense against viral infection. Posttranslational modifications such as ubiquitination regulate diverse molecules in the IFN pathway. To search for the deubiquitinating enzymes (DUBs) involved in the antiviral activity of IFN, we used RNA interference screening to identify a human DUB, ubiquitin-specific protease (USP) 13, whose expression modulates the antiviral activity of IFN-α against dengue virus serotype 2 (DEN-2). The signaling events and anti-DEN-2 activities of IFN-α and IFN-γ were reduced in cells with USP13 knockdown but enhanced with USP13 overexpression. USP13 may regulate STAT1 protein because the protein level and stability of STAT1 were increased with USP13 overexpression. Furthermore, STAT1 ubiquitination was reduced in cells with USP13 overexpression and increased with USP13 knockdown regardless of with or without IFN-α treatment. Thus, USP13 positively regulates type I and type II IFN signaling by deubiquitinating and stabilizing STAT1 protein. Overall, to our knowledge, USP13 is the first DUB identified to modulate STAT1 and play a role in the antiviral activity of IFN against DEN-2 replication.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1300225