Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation
Protein inhibitor of activated STAT (PIAS) proteins are activation-suppressing proteins for signal transducer and activator of transcription (STAT), which involves gene transcriptional regulation. The inhibitory mechanism of PIAS proteins in the Janus kinase (JAK)/STAT signaling pathway has been wel...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02392/full |
| _version_ | 1819034071831937024 |
|---|---|
| author | Guo-Juan Niu Ji-Dong Xu Wen-Jie Yuan Jie-Jie Sun Ming-Chong Yang Zhong-Hua He Xiao-Fan Zhao Jin-Xing Wang Jin-Xing Wang |
| author_facet | Guo-Juan Niu Ji-Dong Xu Wen-Jie Yuan Jie-Jie Sun Ming-Chong Yang Zhong-Hua He Xiao-Fan Zhao Jin-Xing Wang Jin-Xing Wang |
| author_sort | Guo-Juan Niu |
| collection | DOAJ |
| description | Protein inhibitor of activated STAT (PIAS) proteins are activation-suppressing proteins for signal transducer and activator of transcription (STAT), which involves gene transcriptional regulation. The inhibitory mechanism of PIAS proteins in the Janus kinase (JAK)/STAT signaling pathway has been well studied in mammals and Drosophila. However, the roles of PIAS in crustaceans are unclear. In the present study, we identified PIAS in kuruma shrimp Marsupenaeus japonicus and found that its relative expression could be induced by Vibrio anguillarum stimulation. To explore the function of PIAS in shrimp infected with V. anguillarum, we performed an RNA interference assay. After knockdown of PIAS expression in shrimp subjected to V. anguillarum infection, bacterial clearance was enhanced and the survival rate increased compared with those in the control shrimp (dsGFP injection). Simultaneously, the expression levels of antimicrobial peptides (AMPs), including anti-lipopolysaccharide factor (ALF) A1, C1, C2, and CruI-1, increased. Further study revealed that knockdown of PIAS also enhanced STAT phosphorylation and translocation. Pulldown assay indicated that PIAS interacts with activated STAT in shrimp. In conclusion, PIAS negatively regulates JAK/STAT signaling by inhibiting the phosphorylation and translocation of STAT through the interaction between PIAS and STAT, which leads to the reduction of AMP expression in shrimp. Our results revealed a new mechanism of PIAS-mediated gene regulation of the STAT signal pathway. |
| first_indexed | 2024-12-21T07:27:54Z |
| format | Article |
| id | doaj.art-05b5fdb2ccf34200a55070209e29db84 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T07:27:54Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-05b5fdb2ccf34200a55070209e29db842022-12-21T19:11:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02392390956Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and TranslocationGuo-Juan Niu0Ji-Dong Xu1Wen-Jie Yuan2Jie-Jie Sun3Ming-Chong Yang4Zhong-Hua He5Xiao-Fan Zhao6Jin-Xing Wang7Jin-Xing Wang8Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao, ChinaProtein inhibitor of activated STAT (PIAS) proteins are activation-suppressing proteins for signal transducer and activator of transcription (STAT), which involves gene transcriptional regulation. The inhibitory mechanism of PIAS proteins in the Janus kinase (JAK)/STAT signaling pathway has been well studied in mammals and Drosophila. However, the roles of PIAS in crustaceans are unclear. In the present study, we identified PIAS in kuruma shrimp Marsupenaeus japonicus and found that its relative expression could be induced by Vibrio anguillarum stimulation. To explore the function of PIAS in shrimp infected with V. anguillarum, we performed an RNA interference assay. After knockdown of PIAS expression in shrimp subjected to V. anguillarum infection, bacterial clearance was enhanced and the survival rate increased compared with those in the control shrimp (dsGFP injection). Simultaneously, the expression levels of antimicrobial peptides (AMPs), including anti-lipopolysaccharide factor (ALF) A1, C1, C2, and CruI-1, increased. Further study revealed that knockdown of PIAS also enhanced STAT phosphorylation and translocation. Pulldown assay indicated that PIAS interacts with activated STAT in shrimp. In conclusion, PIAS negatively regulates JAK/STAT signaling by inhibiting the phosphorylation and translocation of STAT through the interaction between PIAS and STAT, which leads to the reduction of AMP expression in shrimp. Our results revealed a new mechanism of PIAS-mediated gene regulation of the STAT signal pathway.https://www.frontiersin.org/article/10.3389/fimmu.2018.02392/fullprotein inhibitor of activated STATsignal transducer and activator of transcriptionsignaling pathwayantimicrobial peptideMarsupenaeus japonicus |
| spellingShingle | Guo-Juan Niu Ji-Dong Xu Wen-Jie Yuan Jie-Jie Sun Ming-Chong Yang Zhong-Hua He Xiao-Fan Zhao Jin-Xing Wang Jin-Xing Wang Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation Frontiers in Immunology protein inhibitor of activated STAT signal transducer and activator of transcription signaling pathway antimicrobial peptide Marsupenaeus japonicus |
| title | Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation |
| title_full | Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation |
| title_fullStr | Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation |
| title_full_unstemmed | Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation |
| title_short | Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation |
| title_sort | protein inhibitor of activated stat pias negatively regulates the jak stat pathway by inhibiting stat phosphorylation and translocation |
| topic | protein inhibitor of activated STAT signal transducer and activator of transcription signaling pathway antimicrobial peptide Marsupenaeus japonicus |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02392/full |
| work_keys_str_mv | AT guojuanniu proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT jidongxu proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT wenjieyuan proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT jiejiesun proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT mingchongyang proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT zhonghuahe proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT xiaofanzhao proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT jinxingwang proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation AT jinxingwang proteininhibitorofactivatedstatpiasnegativelyregulatesthejakstatpathwaybyinhibitingstatphosphorylationandtranslocation |